Submissions for variant NM_000135.4(FANCA):c.3583C>T (p.Arg1195Trp)

gnomAD frequency: 0.00035  dbSNP: rs143642304

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000204450	SCV000262267	likely benign	Fanconi anemia	2024-01-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001115378	SCV001273350	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.
Baylor Genetics	RCV001115378	SCV001482547	uncertain significance	Fanconi anemia complementation group A	2020-12-22	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genetic Services Laboratory, University of Chicago	RCV000120942	SCV002072319	uncertain significance	not specified	2020-09-10	criteria provided, single submitter	clinical testing	DNA sequence analysis of the FANCA gene demonstrated a sequence change, c.3583C>T, in exon 36 that results in an amino acid change, p.Arg1195Trp. This sequence change does not appear to have been previously described in patients with FANCA-related disorders and has described in the gnomAD database with a frequency of 0.4% in the Ashkenazi Jewish population (dbSNP rs143642304). The p.Arg1195Trp change affects a poorly conserved amino acid residue located in a domain of the FANCA protein that is not known to be functional. The p.Arg1195Trp 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.Arg1195Trp change remains unknown at this time.
Sema4, Sema4	RCV000204450	SCV002535014	likely benign	Fanconi anemia	2021-04-23	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001115378	SCV004017558	likely benign	Fanconi anemia complementation group A	2023-07-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003407512	SCV004143594	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	FANCA: BP4, BS2
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003407512	SCV004218570	likely benign	not provided	2023-06-08	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV003407512	SCV004224280	uncertain significance	not provided	2022-06-07	criteria provided, single submitter	clinical testing
ITMI	RCV000120942	SCV000085110	not provided	not specified	2013-09-19	no assertion provided	reference population
PreventionGenetics, part of Exact Sciences	RCV003952597	SCV004775712	likely benign	FANCA-related disorder	2022-02-10	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).