ClinVar Miner

Submissions for variant NM_001018113.3(FANCB):c.2521A>G (p.Lys841Glu)

gnomAD frequency: 0.00001  dbSNP: rs767194178
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001910110 SCV002184013 uncertain significance Fanconi anemia 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces lysine with glutamic acid at codon 841 of the FANCB protein (p.Lys841Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is present in population databases (rs767194178, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with FANCB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002266058 SCV002548108 uncertain significance not specified 2022-05-27 criteria provided, single submitter clinical testing Variant summary: FANCB c.2521A>G (p.Lys841Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.6e-06 in 178946 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2521A>G in individuals affected with Fanconi Anemia and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002425233 SCV002742037 uncertain significance Inborn genetic diseases 2014-11-24 criteria provided, single submitter clinical testing The p.K841E variant (also known as c.2521A>G), located in coding exon 8 of the FANCB gene, results from an A to G substitution at nucleotide position 2521. The lysine at codon 841 is replaced by glutamic acid, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples with coverage at this position. This amino acid position is not conserved on limited sequence alignment. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.

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