Submissions for variant NM_000135.4(FANCA):c.761GAA[1] (p.Arg255del)

dbSNP: rs555210441

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000824515	SCV000965415	uncertain significance	Fanconi anemia	2024-10-23	criteria provided, single submitter	clinical testing	This variant, c.764_766del, results in the deletion of 1 amino acid(s) of the FANCA protein (p.Arg255del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs555210441, gnomAD 0.02%). This variant has been observed in individual(s) with Fanconi anemia (PMID: 9371798). ClinVar contains an entry for this variant (Variation ID: 134292). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Sema4, Sema4	RCV000824515	SCV002535073	uncertain significance	Fanconi anemia	2022-01-26	criteria provided, single submitter	curation
Revvity Omics, Revvity	RCV001274649	SCV003833898	uncertain significance	Fanconi anemia complementation group A	2019-05-31	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477513	SCV004218642	uncertain significance	not provided	2024-10-18	criteria provided, single submitter	clinical testing	The FANCA c.764_766del (p.Arg255del) variant has been reported in the published literature in individual(s) with Fanconi anemia (PMID: 9371798 (1997)) as well as in reportedly healthy individuals (PMID: 24728327 (2014), 29641532 (2018)). The frequency of this variant in the general population, 0.00028 (7/24964 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.
Mayo Clinic Laboratories, Mayo Clinic	RCV003477513	SCV004224296	uncertain significance	not provided	2022-09-13	criteria provided, single submitter	clinical testing	PM4
ITMI	RCV000120965	SCV000085133	not provided	not specified	2013-09-19	no assertion provided	reference population
Natera, Inc.	RCV001274649	SCV001459003	uncertain significance	Fanconi anemia complementation group A	2020-09-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004742268	SCV005341288	uncertain significance	FANCA-related disorder	2024-07-17	no assertion criteria provided	clinical testing	The FANCA c.764_766delGAA variant is predicted to result in an in-frame deletion (p.Arg255del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.028% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.