ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.558C>G (p.His186Gln)

dbSNP: rs149159377
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001300970 SCV001490125 uncertain significance Fanconi anemia 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces histidine with glutamine at codon 186 of the FANCA protein (p.His186Gln). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with FANCA-related conditions. 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 glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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.
Fulgent Genetics, Fulgent Genetics RCV002499559 SCV002783391 uncertain significance Fanconi anemia complementation group A 2022-03-04 criteria provided, single submitter clinical testing
Natera, Inc. RCV001300970 SCV002090753 uncertain significance Fanconi anemia 2021-05-04 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004727102 SCV005338957 uncertain significance FANCA-related disorder 2024-08-29 no assertion criteria provided clinical testing The FANCA c.558C>G variant is predicted to result in the amino acid substitution p.His186Gln. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1004288/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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