Submissions for variant NM_000135.4(FANCA):c.3427C>G (p.Leu1143Val)

gnomAD frequency: 0.00048  dbSNP: rs61753269

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000474415	SCV000547783	benign	Fanconi anemia	2024-01-25	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV002293419	SCV002010184	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120940	SCV002065177	uncertain significance	not specified	2019-06-26	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000474415	SCV002535005	likely benign	Fanconi anemia	2021-05-14	criteria provided, single submitter	curation
GeneDx	RCV002293419	SCV002586616	uncertain significance	not provided	2023-05-16	criteria provided, single submitter	clinical testing	Identified in the heterozygous state in individuals with breast cancer, but familial segregation information was limited and additional clinical information was not included (Seal et al., 2003; Litim et al., 2013); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 24728327, 14695169, 23021409)
CeGaT Center for Human Genetics Tuebingen	RCV002293419	SCV004143596	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	FANCA: BP4
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV003444203	SCV004171525	uncertain significance	Fanconi anemia complementation group A	2023-10-31	criteria provided, single submitter	clinical testing	The FANCA c.3427C>G (p.Leu1143Val) missense change has a maximum non-founder subpopulation frequency of 0.070% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the role of this variant in Fanconi anemia. It has therefore been classified as of uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002293419	SCV004218560	likely benign	not provided	2023-03-08	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV002293419	SCV004224281	uncertain significance	not provided	2023-01-17	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004619201	SCV005116038	likely benign	Inborn genetic diseases	2024-04-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ITMI	RCV000120940	SCV000085108	not provided	not specified	2013-09-19	no assertion provided	reference population
PreventionGenetics, part of Exact Sciences	RCV003965014	SCV004782351	likely benign	FANCA-related disorder	2022-03-09	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).