ClinVar Miner

Submissions for variant NM_000075.4(CDK4):c.777G>A (p.Ser259=)

gnomAD frequency: 0.00001  dbSNP: rs3211622
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000422425 SCV000512542 benign not specified 2015-09-15 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000569838 SCV000669086 likely benign Hereditary cancer-predisposing syndrome 2015-04-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000589016 SCV000695330 likely benign not provided 2016-04-11 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a synonymous change involving a non-conserved nucleotide with 4/5 in silico tools via Alamut predicting no significant effect on splicing, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 4/120492 (1/30120), which exceeds the predicted maximum expected allele frequency for a pathogenic CDK4 variant of 1/50000. However, these observations need to be cautiously considered due to the cohort including individuals that could harbor a CDK4-causing phenotype. In addition, the variant of interest, to our knowledge, has not been reported in affected individuals via publications and/or reputable databases/clinical laboratories. Therefore, taking all available lines of evidence into consideration the variant of interest is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV001443022 SCV001645982 likely benign Familial melanoma 2025-01-23 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV004791449 SCV005405072 benign Melanoma, cutaneous malignant, susceptibility to, 3 2024-09-26 criteria provided, single submitter clinical testing This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.

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