Submissions for variant NM_030777.4(SLC2A10):c.674G>A (p.Arg225His)

gnomAD frequency: 0.00302  dbSNP: rs34295241

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001002470	SCV000290950	likely benign	Arterial tortuosity syndrome	2024-01-11	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001798741	SCV000317888	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-04-20	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Eurofins Ntd Llc (ga)	RCV000338554	SCV000333791	benign	not specified	2015-08-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000338554	SCV000514668	benign	not specified	2015-07-29	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.
CeGaT Center for Human Genetics Tuebingen	RCV000585432	SCV000693059	uncertain significance	not provided	2017-07-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001002470	SCV001160418	likely benign	Arterial tortuosity syndrome	2019-04-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000338554	SCV001339252	likely benign	not specified	2024-01-15	criteria provided, single submitter	clinical testing	Variant summary: SLC2A10 c.674G>A (p.Arg225His) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 250864 control chromosomes, including 3 homozygotes, predominantly at a frequency of 0.0089 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 5.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Arterial Tortuosity Syndrome phenotype (0.0016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.674G>A has been reported in the literature in at least one homozygous individual affected with Arterial Tortuosity Syndrome (e.g., Beyens_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Arterial Tortuosity Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29323665). ClinVar contains an entry for this variant (Variation ID: 241606). Based on the evidence outlined above, the variant was classified as likely benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798741	SCV002043616	benign	Familial thoracic aortic aneurysm and aortic dissection	2019-05-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000338554	SCV001807502	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000585432	SCV001967981	likely benign	not provided		no assertion criteria provided	clinical testing