Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001271641 | SCV001727622 | benign | Spongy degeneration of central nervous system | 2022-10-21 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002363205 | SCV002661491 | benign | Inborn genetic diseases | 2015-06-18 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469308 | SCV002765953 | benign | not specified | 2022-11-12 | criteria provided, single submitter | clinical testing | Variant summary: ASPA c.703G>A (p.Glu235Lys) 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 0.0017 in 282776 control chromosomes (gnomAD), predominantly at a frequency of 0.019 within the African or African-American subpopulation in the gnomAD database, including 9 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2.4 fold of the estimated maximal expected allele frequency for a pathogenic variant in ASPA causing Canavan Disease phenotype (0.0079), 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.703G>A in individuals affected with Canavan Disease and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance and two as benign. Based on the evidence outlined above, the variant was classified as benign. |
| Breakthrough Genomics, |
RCV004710194 | SCV005252101 | benign | not provided | criteria provided, single submitter | not provided | ||
| Natera, |
RCV001271641 | SCV001452943 | uncertain significance | Spongy degeneration of central nervous system | 2017-04-25 | no assertion criteria provided | clinical testing |