ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3764A>C (p.Glu1255Ala)

gnomAD frequency: 0.00002  dbSNP: rs373998809
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001237015 SCV001409762 uncertain significance Fanconi anemia 2022-10-06 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1255 of the FANCA protein (p.Glu1255Ala). This variant is present in population databases (rs373998809, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 963048). 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 disruptive. 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.
PreventionGenetics, part of Exact Sciences RCV003405431 SCV004106126 uncertain significance FANCA-related condition 2022-10-03 criteria provided, single submitter clinical testing The FANCA c.3764A>C variant is predicted to result in the amino acid substitution p.Glu1255Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-89809209-T-G) and is classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/963048/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001237015 SCV002092501 uncertain significance Fanconi anemia 2020-03-31 no assertion criteria provided clinical testing

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