Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000680968 | SCV000808417 | benign | not provided | 2020-04-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000680968 | SCV001002876 | benign | not provided | 2024-01-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193987 | SCV001363192 | benign | not specified | 2019-11-25 | criteria provided, single submitter | clinical testing | Variant summary: A2ML1 c.2032G>T (p.Val678Leu) 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 0.00071 in 249516 control chromosomes, predominantly at a frequency of 0.0099 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 2475 fold of 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. A ClinVar submission (evaluation after 2014) cites variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. |