Submissions for variant NM_030777.4(SLC2A10):c.1609A>G (p.Ile537Val)

gnomAD frequency: 0.02113  dbSNP: rs7348121

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000128132	SCV000171724	benign	not specified	2013-02-01	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics, part of Exact Sciences	RCV000128132	SCV000314734	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000770711	SCV000317374	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-02-03	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.
Illumina Laboratory Services, Illumina	RCV000363470	SCV000434174	benign	Arterial tortuosity syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000363470	SCV000560123	benign	Arterial tortuosity syndrome	2025-02-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000363470	SCV000605159	benign	Arterial tortuosity syndrome	2020-10-13	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000770711	SCV000902188	benign	Familial thoracic aortic aneurysm and aortic dissection	2016-03-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000128132	SCV001338203	benign	not specified	2020-02-17	criteria provided, single submitter	clinical testing	Variant summary: SLC2A10 c.1609A>G (p.Ile537Val) 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 0.0061 in 251458 control chromosomes, predominantly at a frequency of 0.067 within the African or African-American subpopulation in the gnomAD database, including 46 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 42-fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Aortopathy phenotype (0.0016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1609A>G in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV004717065	SCV005313997	benign	not provided		criteria provided, single submitter	not provided