Submissions for variant NM_000135.4(FANCA):c.862G>T (p.Glu288Ter)

gnomAD frequency: 0.00006  dbSNP: rs148100796

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000474583	SCV000547763	pathogenic	Fanconi anemia	2024-10-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu288*) in the FANCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCA are known to be pathogenic (PMID: 19367192). This variant is present in population databases (rs148100796, gnomAD 0.01%). This premature translational stop signal has been observed in individuals with Fanconi anemia (PMID: 10521298, 12697994, 22778927). ClinVar contains an entry for this variant (Variation ID: 134239). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genetic Services Laboratory, University of Chicago	RCV001818291	SCV002072103	pathogenic	not provided	2017-07-28	criteria provided, single submitter	clinical testing	This sequence change is predicted to result in an abnormal transcript, which may be degraded, or may lead to the production of a truncated FANCA protein with potentially abnormal function. This pathogenic sequence change has previously been described in patients with Fanconi anemia (Morgan NV, et al., 1999; Savino M et al., 1997; De Rocco D et al., 2014; Nicchia E, et al., 2015).
GeneDx	RCV001818291	SCV002762317	pathogenic	not provided	2022-12-07	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24728327, 25525159, 10521298, 12697994, 22778927, 31263571)
Fulgent Genetics, Fulgent Genetics	RCV000665641	SCV002812556	pathogenic	Fanconi anemia complementation group A	2021-08-26	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV001818291	SCV004026681	pathogenic	not provided	2025-03-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000665641	SCV004196007	pathogenic	Fanconi anemia complementation group A	2024-03-22	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001818291	SCV005051573	pathogenic	not provided	2024-05-01	criteria provided, single submitter	clinical testing	FANCA: PVS1, PM2, PM3
ITMI	RCV000120912	SCV000085080	not provided	not specified	2013-09-19	no assertion provided	reference population
Counsyl	RCV000665641	SCV000789794	pathogenic	Fanconi anemia complementation group A	2017-02-21	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000474583	SCV002095092	pathogenic	Fanconi anemia	2020-11-18	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925189	SCV004747139	pathogenic	FANCA-related disorder	2024-02-29	no assertion criteria provided	clinical testing	The FANCA c.862G>T variant is predicted to result in premature protein termination (p.Glu288*). This variant has been reported previously to be causative for Fanconi anemia (Morgan et al. 1999. PubMed ID: 10521298; Gille et al. 2012. PubMed ID: 22778927). This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD and is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/134239/). Nonsense variants in FANCA are expected to be pathogenic. This variant is interpreted as pathogenic.