ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1899A>C (p.Glu633Asp)

gnomAD frequency: 0.00004  dbSNP: rs768520283
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000543652 SCV000626157 uncertain significance Fanconi anemia 2022-10-25 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 633 of the FANCA protein (p.Glu633Asp). This variant is present in population databases (rs768520283, gnomAD 0.02%). 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: 456089). 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 aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Fulgent Genetics, Fulgent Genetics RCV002497049 SCV002783870 uncertain significance Fanconi anemia complementation group A 2022-03-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV004023745 SCV004869458 uncertain significance Inborn genetic diseases 2023-12-19 criteria provided, single submitter clinical testing The c.1899A>C (p.E633D) alteration is located in exon 21 (coding exon 21) of the FANCA gene. This alteration results from a A to C substitution at nucleotide position 1899, causing the glutamic acid (E) at amino acid position 633 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV002497049 SCV005402111 uncertain significance Fanconi anemia complementation group A 2023-12-14 criteria provided, single submitter clinical testing The FANCA c.1899A>C (p.Glu633Asp) missense change has a maximum subpopulation frequency of 0.016% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Natera, Inc. RCV000543652 SCV002092665 uncertain significance Fanconi anemia 2019-10-28 no assertion criteria provided clinical testing

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