Submissions for variant NM_001018113.3(FANCB):c.2342A>G (p.Glu781Gly)

gnomAD frequency: 0.00010  dbSNP: rs140363445

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000694135	SCV000822566	benign	Fanconi anemia	2024-01-12	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001167743	SCV001330273	likely benign	Fanconi anemia complementation group B	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001169616	SCV001332361	likely benign	VACTERL association, X-linked, with or without hydrocephalus	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001756194	SCV001987607	uncertain significance	not provided	2023-09-08	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30404791, 29654263, 31721781)
Genetic Services Laboratory, University of Chicago	RCV001816713	SCV002066709	uncertain significance	not specified	2020-11-30	criteria provided, single submitter	clinical testing	This sequence change does not appear to have been previously described in patients with FANCB-related disorders and has been described in the gnomAD database with a low population frequency of 0.0034% (dbSNP rs140363445). The p.Glu781Gly change affects a poorly conserved amino acid residue located in a domain of the FANCB protein that is not known to be functional. The p.Glu781Gly substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Glu781Gly change remains unknown at this time.
Sema4, Sema4	RCV000694135	SCV002534241	likely benign	Fanconi anemia	2021-11-01	criteria provided, single submitter	curation