ClinVar Miner

Submissions for variant NM_144670.6(A2ML1):c.2032G>T (p.Val678Leu)

gnomAD frequency: 0.00280  dbSNP: rs148198269
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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, LabCorp 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.

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