Case: Family 2 Kismet Proband, Turkish, male

CasePresentingHPOs: HP:0000407, HP:0002240, HP:0004322, HP:0025289, HP:0033176, HP:0100727

CasePresentingHPOsFreeText: Rapidly growing orbital mass with SHML histopathology. Retropharyngeal lymphadenopathy. Filling of lymph node sinuses with histiocytes, plasma cells and lymphocytes. Histiocytes had a benign appearance, were CD-1a negative but positive for CD68 and S-100.

CaseNOTHPOs:

CaseNOTHPOSFreeText:

CasePreviousTesting: direct sequencing of PRF1 and UNC5B

CaseGenotypingMethod: genotyping (genome-wide linkage scan was performed using Affymetrix 250k SNP arrays), direct sequencing, PCR

Variant: p.Gly437Arg; p.Phe103X

ClinVarID: or CAID: 565; 30947

gnomAD: The missense variant G437R is present in gnomAD v4.0.0 with a MAF=0.00006666 (4/60002 alleles) in the Admixed American population and 0 homozygotes.

The nonsense variant, p.Phe103Ter found in exon 2/6, is present in gnomAD v4.0.0 with a MAF=0.0005201 (3/5768 alleles) in the Middle Eastern population and 0 homozygotes.

AddCaseInfo: 2 affected brothers

PreviouslyPublished: 16118898

VariantEvidence: Functional characterization of G437R in Xenopus oocytes showed that transport activity was approximately half of WT SLC29A3. Studies in NIH 3T3 fibroblasts demonstrated accelerated turnover of the G437R mutant compared to WT, suggesting decreased stability (Kang et al. 2010; PMID: 20595384)