Hypothesis

15 Matching Annotations

Apr 2025
onlinelibrary.wiley.com onlinelibrary.wiley.com

Management of a patient with acute myeloid leukaemia with a diagnosis of type 2 von Willebrand disease and a novel variant within the von Willebrand factor (VWF) gene

1
1. krisBussey97 07 Apr 2025
  
  in Public
  
  Disease: Von-willebrand Disease (Type 2A)
  
  Patient: 50 yo female
  
  Variant: VWF NM_000552.5 c:4232_4249del p.(Val411_Ile416del), Exon 28, heterozygous variant
  
  According to this paper, ACMG-AMP guidelines for interpreting this variant resulted in classification of likely pathogenic
  
  Phenotypes: increased bruising, fatigue, recurrent sinusitis, menorrhagia, neutropenia, anaemia. Reduction in high-molecular-weight multimers
  
  Family: segregation analysis showed two affected family members had the variant and two unaffected family members did not have variant.
  
  Note: Patient also has diagnosed Acute Myeloid Leukaemia (AML) NM_000546.6(TP53):c704A>G p.(Asn235Ser), listed as VUS and found by NGS
  
  VWF exon 28 deletion variant VWD 2A AML TP53 variant likely pathogenic
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deletion variant

VWF exon 28

AML TP53 variant

VWD 2A

likely pathogenic

Annotators

krisBussey97

URL

onlinelibrary.wiley.com/doi/10.1111/bjh.18390
May 2022
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Clinicopathologic and molecular analysis of embryonal rhabdomyosarcoma of the genitourinary tract: evidence for a distinct DICER1-associated subgroup

1
1. nslotnick 02 May 2022
  
  in Public
  
  Embryonal rhabdomyosarcoma (ERMS) of the uterus has recently been shown to frequently harbor DICER1 mutations.
  
  HGNCID:
  
  GeneName: DICER1 PMID (PubMed ID): 33846547 Inheritance Pattern: Non- inheritance(DNA methylation) Disease Entity: Embryonal rhabdomyosarcoma (ERMS) Mutation: c5113G>A Mutation: c.4420A>G Mutation: c.5428G>T Mutation: c.5125G > A Mutation: c.4267G>T Mutation: c.3580delA Mutation: 5428 G>C Mutation: c.5438 A> C Zygosity: Some Cases displayed homozygosity Variant: Clinvar ID not identified Family Information: not identified case mut: f 28-67 case wt: m&f 0.5-19 pathogenicity: only 2 of 17 patients died from disease
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Family Information: not identified

Mutation: c.5428G>T

Mutation: c5113G>A

Mutation: c.5438 A> C

Mutation: c.4267G>T

Disease Entity: Embryonal rhabdomyosarcoma (ERMS)

Inheritance Pattern: Non- inheritance(DNA methylation)

Variant: Clinvar ID not identified

Mutation: 5428 G>C

Zygosity: Some Cases displayed homozygosity

Mutation: c.3580delA

Mutation: c.4420A>G

GeneName: DICER1

Mutation: c.5125G > A

case wt: m&f 0.5-19

pathogenicity: only 2 of 17 patients died from disease

PMID (PubMed ID): 33846547

case mut: f 28-67

Annotators

nslotnick

URL

ncbi.nlm.nih.gov/pmc/articles/PMC8295035/pdf/41379_2021_Article_804.pdf
Mar 2021
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Functional characterization of 84 PALB2 variants of uncertain significance

2
1. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  Results for individual PALB2 variants were normalized relative to WT-PALB2 and the p.Tyr551ter (p.Y551X) truncating variant on a 1:5 scale with the fold change in GFP-positive cells for WT set at 5.0 and fold change GFP-positive cells for p.Y551X set at 1.0. The p.L24S (c.71T>C), p.L35P (c.104T>C), p.I944N (c.2831T>A), and p.L1070P (c.3209T>C) variants and all protein-truncating frame-shift and deletion variants tested were deficient in HDR activity, with normalized fold change <2.0 (approximately 40% activity) (Fig. 1a).
  
  AssayResult: 6.6
  
  AssayResultAssertion: Normal
  
  StandardErrorMean: 0.8
  
  CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:28 CAID:CA288441 ClinVarID:126647
2. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  A total of 84 PALB2 patient-derived missense variants reported in ClinVar, COSMIC, and the PALB2 LOVD database were selected
  
  HGVS: NM_024675.3:c.232G>A p.(Val78Ile)
  
  CGType:Variant CG:BulkAnnotation Variant:28 ClinVarID:126647 CAID:CA288441
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CGType:Variant

FuncAssay:1

CAID:CA288441

CG:BulkAnnotation

ClinVarID:126647

Variant:28

CGType:FunctionalAssayResult

Annotators

shannon_mcnulty

URL

ncbi.nlm.nih.gov/pmc/articles/PMC7056643/
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

A global functional analysis of missense mutations reveals two major hotspots in the PALB2 tumor suppressor

2
1. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  SUPPLEMENTARY DATA
  
  AssayResult: 96.63
  
  AssayResultAssertion: Not reported
  
  PValue: > 0.9999
  
  Comment: Exact values reported in Table S3.
  
  CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:28 CAID:CA269610 ClinVarID:126731
2. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  To this end, 44 missense variants found in breast cancer patients were identified in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar) and/or selected by literature curation based on their frequency of description or amino acid substitution position in the protein (Supplemental Table S1).
  
  HGVS: NM_024675.3:c.3306C>G p.(Ser1102Arg)
  
  CGType:Variant CG:BulkAnnotation Variant:28 ClinVarID:126731 CAID:CA269610
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CGType:Variant

ClinVarID:126731

FuncAssay:1

CG:BulkAnnotation

Variant:28

CAID:CA269610

CGType:FunctionalAssayResult

Annotators

shannon_mcnulty

URL

ncbi.nlm.nih.gov/pmc/articles/PMC6847799/
www.nature.com www.nature.com

Functional analysis of genetic variants in the high-risk breast cancer susceptibility gene PALB2

4
1. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  Source Data
  
  AssayResult: 112.08
  
  AssayResultAssertion: Not reported
  
  ReplicateCount: 2
  
  StandardErrorMean: 4.1
  
  Comment: Exact values reported in “Source Data” file.
  
  CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:3 Variant:28 CAID:CA196017 ClinVarID:186840
2. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  Source Data
  
  AssayResult: 94.54
  
  AssayResultAssertion: Not reported
  
  ReplicateCount: 2
  
  StandardErrorMean: 19.94
  
  Comment: Exact values reported in “Source Data” file.
  
  CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:2 Variant:28 CAID:CA196017 ClinVarID:186840
3. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  Source Data
  
  AssayResult: 106.23
  
  AssayResultAssertion: Not reported
  
  ReplicateCount: 2
  
  StandardDeviation: 14.57
  
  StandardErrorMean: 10.3
  
  Comment: Exact values reported in “Source Data” file.
  
  CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:28 CAID:CA196017 ClinVarID:186840
4. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  We, therefore, analyzed the effect of 48 PALB2 VUS (Fig. 2a, blue) and one synthetic missense variant (p.A1025R) (Fig. 2a, purple)29 on PALB2 function in HR.
  
  HGVS: NM_024675.3:c.2792T>G p.(L931R)
  
  CGType:Variant CG:BulkAnnotation Variant:28 ClinVarID:186840 CAID:CA196017
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CGType:Variant

ClinVarID:186840

CAID:CA196017

FuncAssay:1

FuncAssay:2

FuncAssay:3

CG:BulkAnnotation

Variant:28

CGType:FunctionalAssayResult

Annotators

shannon_mcnulty

URL

nature.com/articles/s41467-019-13194-2
www.cell.com www.cell.com

High-Throughput Reclassification of SCN5A Variants

2
1. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  Most Suspected Brugada Syndrome Variants Had (Partial) Loss of Function
  
  AssayResult: 0.8
  
  AssayResultAssertion: Abnormal
  
  ReplicateCount: 23
  
  StandardErrorMean: 0.6
  
  Comment: This variant had loss of function of peak current (<10% of wildtype), therefore it was considered abnormal (in vitro features consistent with Brugada Syndrome Type 1). (Personal communication: A. Glazer)
  
  CGType:FunctionalAssayResult CG:BulkAnnotation FuncAssay:1 Variant:28 CAID:CA016384 ClinVarID:67747
2. shannon_mcnulty 18 Mar 2021
  
  in Public
  
  we selected 73 previously unstudied variants: 63 suspected Brugada syndrome variants and 10 suspected benign variants
  
  HGVS: NM_198056.2:c.2674T>A p.(Phe892Ile)
  
  CGType:Variant CG:BulkAnnotation Variant:28 ClinVarID:67747 CAID:CA016384
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Tags

CGType:Variant

ClinVarID:67747

FuncAssay:1

CAID:CA016384

CG:BulkAnnotation

Variant:28

CGType:FunctionalAssayResult

Annotators

shannon_mcnulty

URL

cell.com/ajhg/fulltext/S0002-9297(20)30162-2
Feb 2021
jmg.bmj.com jmg.bmj.com

Blood functional assay for rapid clinical interpretation of germline TP53 variants

3
1. shannon_mcnulty 24 Feb 2021
  
  in Public
  
  Supplemental material
  
  AssayResult: 104
  
  AssayResultAssertion: Normal
  
  Comment: See Table S2 for details
  
  CGType:FunctionalAssayResult FuncAssay:2 Variant:28 CAID:CA16603033 ClinVarID:376612 ValidationControl:Pathogenic
2. shannon_mcnulty 24 Feb 2021
  
  in Public
  
  Supplemental material
  
  AssayResult: 4.2
  
  AssayResultAssertion: Abnormal
  
  Comment: See Table S2 for details
  
  CGType:FunctionalAssayResult FuncAssay:1 Variant:28 CAID:CA16603033 ClinVarID:376612 ValidationControl:Pathogenic
3. shannon_mcnulty 24 Feb 2021
  
  in Public
  
  We analysed a total of 82 blood samples derived from 77 individuals (online supplemental table 3). These 77 individuals corresponded either to new index cases suspected to harbour a pathogenic TP53 variant or to relatives of index cases harbouring TP53 variants.
  
  HGVS: NM_000546.5:c.578A>C p.(His193Pro)
  
  CGType:Variant Variant:28 ClinVarID:376612 CAID:CA16603033
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Tags

CGType:Variant

ValidationControl:Pathogenic

ClinVarID:376612

FuncAssay:1

FuncAssay:2

CAID:CA16603033

Variant:28

CGType:FunctionalAssayResult

Annotators

shannon_mcnulty

URL

jmg.bmj.com/content/early/2020/10/13/jmedgenet-2020-107059