ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.2941T>C (p.Cys981Arg)

gnomAD frequency: 0.00001  dbSNP: rs191943709
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210699 SCV000262829 likely pathogenic Inborn genetic diseases 2014-06-18 criteria provided, single submitter clinical testing The c.2941T>C (p.C981R) alteration is located in exon 30 (coding exon 30) of the FANCA gene. This alteration results from a T to C substitution at nucleotide position 2941, causing the cysteine (C) at amino acid position 981 to be replaced by an arginine (R). Based on data from the NHLBI Exome Sequencing Project (ESP), the c.2941T>C alteration was not observed among 6,498 individuals tested (0.0%). This variant was previously reported in the Database of Single Nucleotide Polymorphisms (dbSNP) as rs191943709. Based on data from the 1000 Genomes Project, the C allele has an overall frequency of approximately 0.05% (1/2098) total alleles studied. The highest observed frequency was 0.54% (1/184) Southern Han Chinese alleles. The C981 amino acid position is completely conserved in available vertebrate species. This alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Based on the available evidence, this alteration is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000458460 SCV000547735 uncertain significance Fanconi anemia 2024-10-26 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 981 of the FANCA protein (p.Cys981Arg). This variant is present in population databases (rs191943709, gnomAD 0.04%). 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: 224986). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt FANCA protein function with a positive predictive value of 95%. 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.
Counsyl RCV000675145 SCV000800742 uncertain significance Fanconi anemia complementation group A 2018-03-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000675145 SCV005644425 uncertain significance Fanconi anemia complementation group A 2024-03-26 criteria provided, single submitter clinical testing
Natera, Inc. RCV000675145 SCV001462895 uncertain significance Fanconi anemia complementation group A 2020-09-16 no assertion criteria provided clinical testing
Istanbul Faculty of Medicine, Istanbul University RCV000675145 SCV002524129 pathogenic Fanconi anemia complementation group A 2022-06-06 no assertion criteria provided clinical testing

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