Submissions for variant NM_001018113.3(FANCB):c.781C>T (p.Arg261Ter)

dbSNP: rs2147445599

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001927558	SCV002160404	pathogenic	Fanconi anemia	2023-01-20	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1395141). This variant has not been reported in the literature in individuals affected with FANCB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg261*) in the FANCB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCB are known to be pathogenic (PMID: 15502827, 23613520).
Neuberg Centre For Genomic Medicine, NCGM	RCV004555628	SCV005044797	likely pathogenic	Fanconi anemia complementation group B		criteria provided, single submitter	clinical testing	The stop gained c.781C>T p.Arg261Ter variant in FANCB gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Arg261Ter variant is novel not in any individuals in gnomAD Exomes and is novel not in any individuals in 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.781C>T in FANCB is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in FANCB are known to be pathogenic Chandrasekharappa SC et al. 2013. Functional studies are required to prove the pathogenicity for the variant, for these reasons, this variant has been classified as Likely Pathogenic.