ClinVar Miner

Submissions for variant NM_020937.4(FANCM):c.2258A>G (p.Asp753Gly)

dbSNP: rs756438082
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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 RCV000630870 SCV000751841 uncertain significance Fanconi anemia 2023-11-17 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 753 of the FANCM protein (p.Asp753Gly). This variant is present in population databases (rs756438082, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with FANCM-related conditions. ClinVar contains an entry for this variant (Variation ID: 526349). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Genetic Services Laboratory, University of Chicago RCV001821774 SCV002065254 uncertain significance not specified 2021-05-03 criteria provided, single submitter clinical testing DNA sequence analysis of the FANCM gene demonstrated a sequence change, c.2258A>G, in exon 13 that results in an amino acid change, p.Asp753Gly. This sequence change does not appear to have been previously described in patients with FANCM-related disorders. This sequence change has been described in the gnomAD database with a low frequency of 0.072% in the south Asian subpopulation (dbSNP rs756438082). The p.Asp753Gly change affects a moderately conserved amino acid residue of the FANCM protein. The p.Asp753Gly substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to the lack of functional studies, the clinical significance of the p.Asp753Gly change remains unknown at this time.

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