Submissions for variant NM_030777.4(SLC2A10):c.1559G>A (p.Ser520Asn)

gnomAD frequency: 0.00007  dbSNP: rs573480396

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000836031	SCV000977856	likely benign	not provided	2021-05-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001358748	SCV001554599	likely benign	not specified	2023-05-30	criteria provided, single submitter	clinical testing	Variant summary: SLC2A10 c.1559G>A (p.Ser520Asn) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00036 in 251156 control chromosomes, predominantly at a frequency of 0.0023 within the South Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is higher than the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Arterial Tortuosity Syndrome phenotype (0.0016), suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.1559G>A in individuals affected with Arterial Tortuosity Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as benign (n=1)/likely benign (n=3). Based on the evidence outlined above, the variant was classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001456321	SCV001660099	likely benign	Arterial tortuosity syndrome	2024-11-19	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000836031	SCV001747318	likely benign	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002404473	SCV002704937	benign	Familial thoracic aortic aneurysm and aortic dissection	2020-11-12	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003905405	SCV004727312	likely benign	SLC2A10-related disorder	2021-08-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).