Submissions for variant NM_000135.4(FANCA):c.2390C>T (p.Ala797Val)

gnomAD frequency: 0.00026  dbSNP: rs138248569

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000630849	SCV000751818	likely benign	Fanconi anemia	2024-01-18	criteria provided, single submitter	clinical testing
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV000630849	SCV001737472	uncertain significance	Fanconi anemia	2021-05-20	criteria provided, single submitter	clinical testing	The FANCA c.2390C>T (p.Ala797Val) missense change has a maximum frequency of 0.036% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/16-89836359-G-A?dataset=gnomad_r2_1). In addition, the variant occurs in the homozygous state one time in gnomAD v2.1.1. Six of seven in silico tools predict a benign effect of this variant on protein function (BP4), but to our knowledge these predictions have not been confirmed by functional assays. The variant has been reported as heterozygous in one individual with head and neck carcinoma occurring before age 50 (PMID: 28678401). To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: BP4.
Genetic Services Laboratory, University of Chicago	RCV001821773	SCV002065244	uncertain significance	not specified	2019-11-22	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000630849	SCV002534951	uncertain significance	Fanconi anemia	2021-11-05	criteria provided, single submitter	curation
GeneDx	RCV002461940	SCV002757146	uncertain significance	not provided	2022-05-24	criteria provided, single submitter	clinical testing	Reported in a patient with oropharynx carcinoma who also harbors an additional FANCA variant; however, detailed clinical information was not provided (Chandrasekharappa et al., 2017); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: Zahra2020[research], 28678401)
Natera, Inc.	RCV001271599	SCV001452866	uncertain significance	Fanconi anemia complementation group A	2020-09-16	no assertion criteria provided	clinical testing
GenomeConnect - Invitae Patient Insights Network	RCV001271599	SCV004037535	not provided	Fanconi anemia complementation group A		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 06-13-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.