Submissions for variant NM_000135.4(FANCA):c.4064A>T (p.His1355Leu)

gnomAD frequency: 0.00008  dbSNP: rs145886270

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000299065	SCV000399809	uncertain significance	Fanconi anemia complementation group A	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001242774	SCV001415883	likely benign	Fanconi anemia	2025-01-22	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000299065	SCV001481680	uncertain significance	Fanconi anemia complementation group A	2020-11-23	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab	RCV000299065	SCV001786854	uncertain significance	Fanconi anemia complementation group A	2021-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001731595	SCV001982537	uncertain significance	not provided	2021-08-28	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Ambry Genetics	RCV004021684	SCV004869469	uncertain significance	Inborn genetic diseases	2024-09-26	criteria provided, single submitter	clinical testing	The c.4064A>T (p.H1355L) alteration is located in exon 41 (coding exon 41) of the FANCA gene. This alteration results from a A to T substitution at nucleotide position 4064, causing the histidine (H) at amino acid position 1355 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001731595	SCV005625504	uncertain significance	not provided	2024-10-23	criteria provided, single submitter	clinical testing	The FANCA c.4064A>T (p.His1355Leu) variant has been reported in the published literature in individuals with ovarian cancer (PMID: 32546565 (2021)). The frequency of this variant in the general population, 0.00016 (5/30612 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Fulgent Genetics, Fulgent Genetics	RCV000299065	SCV005642559	uncertain significance	Fanconi anemia complementation group A	2024-05-13	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001242774	SCV002092479	uncertain significance	Fanconi anemia	2019-10-28	no assertion criteria provided	clinical testing