ClinVar Miner

Submissions for variant NM_144670.6(A2ML1):c.1789_1790del (p.Ser597fs)

dbSNP: rs779516620
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001315015 SCV001505569 uncertain significance not provided 2024-07-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser597Cysfs*5) in the A2ML1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in A2ML1 cause disease. This variant is present in population databases (rs779516620, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with A2ML1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282516 SCV002572252 uncertain significance not specified 2022-08-22 criteria provided, single submitter clinical testing Variant summary: A2ML1 c.1789_1790delAG (p.Ser597CysfsX5) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.8e-05 in 248862 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.1789_1790delAG in individuals affected with Noonan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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