Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000553001 | SCV000631806 | likely benign | Alstrom syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001534589 | SCV000732085 | likely benign | not provided | 2021-03-05 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000612301 | SCV000864118 | likely benign | not specified | 2018-11-12 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.8271A>G (alternative name c.8277A>G) alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00047 in 276572 control chromosomes, predominantly at a frequency of 0.0048 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 2.15 fold of the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Cardiomyopathy phenotype (0.0022), suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.8271A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both of them classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Ambry Genetics | RCV002413480 | SCV002675720 | benign | Cardiovascular phenotype | 2019-02-01 | 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. |
| Ce |
RCV001534589 | SCV004154995 | likely benign | not provided | 2022-12-01 | criteria provided, single submitter | clinical testing | ALMS1: BP4, BP7 |