ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.2903A>G (p.Tyr968Cys)

gnomAD frequency: 0.00002  dbSNP: rs752962214
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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 RCV000800281 SCV000939986 uncertain significance Fanconi anemia 2020-08-15 criteria provided, single submitter clinical testing This variant is present in population databases (rs752962214, ExAC 0.02%). This sequence change replaces tyrosine with cysteine at codon 968 of the FANCM protein (p.Tyr968Cys). The tyrosine residue is weakly conserved and there is a large physicochemical difference between tyrosine and cysteine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FANCM-related disease.
GeneDx RCV003235402 SCV003933547 uncertain significance not provided 2024-07-09 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in the germline of an individual with acute lymphoblastic leukemia undergoing whole exome sequencing (PMID: 35739278); This variant is associated with the following publications: (PMID: 35739278)

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