ClinVar Miner

Submissions for variant NM_144670.6(A2ML1):c.2026C>T (p.Arg676Trp)

gnomAD frequency: 0.00026  dbSNP: rs200503836
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000862848 SCV001003410 likely benign not provided 2023-10-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192601 SCV001360840 benign not specified 2019-08-26 criteria provided, single submitter clinical testing Variant summary: A2ML1 c.2026C>T (p.Arg676Trp) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00054 in 244778 control chromosomes, predominantly at a frequency of 0.0013 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 325 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 South Asian origin. c.2026C>T has been reported in the literature in individuals affected with Noonan Syndrome (Vissers_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Noonan Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV000862848 SCV001751251 benign not provided 2020-12-15 criteria provided, single submitter clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000862848 SCV001956597 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000862848 SCV001975324 likely benign not provided no assertion criteria provided clinical testing

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