Submissions for variant NM_000135.4(FANCA):c.2574C>G (p.Ser858Arg)

gnomAD frequency: 0.00567  dbSNP: rs17233141

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000206151	SCV000262266	benign	Fanconi anemia	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000202580	SCV000399841	likely benign	Fanconi anemia complementation group A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000514362	SCV000512960	benign	not provided	2019-05-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24728327, 11091222, 30249500, 21279724, 24082139, 10094191, 27884173, 27153395, 26740942, 15591268, 23021409, 27148581, 30553997, 26799702, 26119737, 29084058, 25231023, 12955722)
Genetic Services Laboratory, University of Chicago	RCV000120929	SCV000594634	benign	not specified	2017-09-01	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514362	SCV000610421	likely benign	not provided	2017-03-20	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000202580	SCV001737170	likely benign	Fanconi anemia complementation group A	2021-05-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000120929	SCV002047241	benign	not specified	2021-06-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000120929	SCV002103357	benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: FANCA c.2574C>G (p.Ser858Arg) results in a non-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 0.01 in 251444 control chromosomes, predominantly at a frequency of 0.032 within the South Asian subpopulation in the gnomAD database, including 26 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 15 fold of the estimated maximal expected allele frequency for a pathogenic variant in FANCA causing Fanconi Anemia phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Ten ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1), likely benign (n=3), benign (n=4) and pathogenic (n=2). Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4	RCV000206151	SCV002534957	benign	Fanconi anemia	2020-07-21	criteria provided, single submitter	curation
CeGaT Center for Human Genetics Tuebingen	RCV000514362	SCV004143605	benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	FANCA: BP4, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003915204	SCV004733489	likely benign	FANCA-related condition	2019-07-16	criteria provided, single submitter	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).
ITMI	RCV000120929	SCV000085097	not provided	not specified	2013-09-19	no assertion provided	reference population
McDonnell Genome Institute, Washington University in St. Louis	RCV000202580	SCV000257331	pathogenic	Fanconi anemia complementation group A	2015-10-22	flagged submission	research
Leiden Open Variation Database	RCV000202580	SCV001425828	pathogenic	Fanconi anemia complementation group A	2020-02-28	flagged submission	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
Natera, Inc.	RCV000202580	SCV001458827	uncertain significance	Fanconi anemia complementation group A	2020-01-09	flagged submission	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000120929	SCV001800807	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000514362	SCV001807935	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000514362	SCV001927739	likely benign	not provided		no assertion criteria provided	clinical testing