Submissions for variant NM_000135.4(FANCA):c.3263C>T (p.Ser1088Phe)

gnomAD frequency: 0.05303  dbSNP: rs17233497

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000120937	SCV000302488	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094408	SCV000399830	benign	Fanconi anemia complementation group A	2018-03-06	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000351747	SCV000558864	benign	Fanconi anemia	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000120937	SCV000603544	benign	not specified	2016-10-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001705888	SCV001900776	benign	not provided	2019-03-12	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31586946, 28864460, 10094191, 27153395, 27884173, 24728327, 20981092, 22995991)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000120937	SCV002051221	benign	not specified	2021-12-18	criteria provided, single submitter	clinical testing	Variant summary: FANCA c.3263C>T (p.Ser1088Phe) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.051 in 250776 control chromosomes in the gnomAD database, including 459 homozygotes. The observed variant frequency is approximately 23.34 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 benign. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as benign.
Sema4, Sema4	RCV000351747	SCV002534994	benign	Fanconi anemia	2020-02-06	criteria provided, single submitter	curation
Breakthrough Genomics, Breakthrough Genomics	RCV001705888	SCV005253318	benign	not provided		criteria provided, single submitter	not provided
ITMI	RCV000120937	SCV000085105	not provided	not specified	2013-09-19	no assertion provided	reference population
Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine	RCV000488415	SCV000494044	uncertain significance	Malignant tumor of prostate	2015-07-01	flagged submission	research
Leiden Open Variation Database	RCV001094408	SCV001426104	pathogenic	Fanconi anemia complementation group A	2020-02-28	flagged submission	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
Natera, Inc.	RCV001094408	SCV001458821	benign	Fanconi anemia complementation group A	2019-08-23	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000120937	SCV001927758	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000120937	SCV001963397	benign	not specified		no assertion criteria provided	clinical testing