Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000858132 | SCV000291420 | benign | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000233054 | SCV000715212 | benign | not specified | 2017-01-31 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000233054 | SCV001362978 | benign | not specified | 2019-12-09 | criteria provided, single submitter | clinical testing | Variant summary: A2ML1 c.590C>T (p.Thr197Ile) results in a non-conservative amino acid change located in the Macroglobulin domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0021 in 249544 control chromosomes, predominantly at a frequency of 0.03 within the African or African-American subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 7500-folds over the estimated maximal expected allele frequency for a pathogenic variant in A2ML1 causing Noonan Syndrome phenotype (4e-06), 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.590C>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
| Ambry Genetics | RCV000233054 | SCV002649566 | likely benign | not specified | 2022-10-03 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
| Breakthrough Genomics, |
RCV000858132 | SCV005230471 | benign | not provided | criteria provided, single submitter | not provided |