ClinVar Miner

Submissions for variant NM_144670.6(A2ML1):c.1834-1G>T

dbSNP: rs1943786459
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001532894 SCV001748681 uncertain significance not specified 2021-06-28 criteria provided, single submitter clinical testing Variant summary: A2ML1 c.1834-1G>T is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 239004 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1834-1G>T in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Furthermore, the validity of this gene relating to a RASopathy phenotype is disputed (ClinGen, 2018). 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 uncertain significance.
PreventionGenetics, part of Exact Sciences RCV003394116 SCV004121082 uncertain significance A2ML1-related disorder 2022-10-17 criteria provided, single submitter clinical testing The A2ML1 c.1834-1G>T variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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