ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.2151G>A (p.Met717Ile)

dbSNP: rs1131660
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001344649 SCV001538715 uncertain significance Fanconi anemia 2020-10-25 criteria provided, single submitter clinical testing 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. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant does not affect mRNA splicing (PMID: 10094191). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with breast cancer (PMID: 14695169). This variant is not present in population databases (ExAC no frequency). This sequence change replaces methionine with isoleucine at codon 717 of the FANCA protein (p.Met717Ile). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant also falls at the last nucleotide of exon 23, which is part of the consensus splice site for this exon.

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