ClinVar Miner

Submissions for variant NM_018062.4(FANCL):c.5C>T (p.Ala2Val)

dbSNP: rs551142193
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001137467 SCV001297408 uncertain significance Fanconi anemia complementation group L 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory, University of Chicago RCV001819842 SCV002064736 uncertain significance not specified 2020-08-21 criteria provided, single submitter clinical testing DNA sequence analysis of the FANCL gene demonstrated a sequence change, c.5C>T, in exon 1 that results in an amino acid change, p.Ala2Val. This sequence change does not appear to have been previously described in patients with FANCL-related disorders and has been described in the gnomAD database in three individuals with an overall population frequency of 0.0012% (dbSNP rs551142193). The p.Ala2Val change affects a poorly conserved amino acid residue located in a domain of the FANCL protein that is not known to be functional. The p.Ala2Val substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Ala2Val change remains unknown at this time.

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