Submissions for variant NM_001018113.3(FANCB):c.1494G>T (p.Lys498Asn)

gnomAD frequency: 0.00005  dbSNP: rs199510538

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000331306	SCV000481919	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000388194	SCV000481920	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genetic Services Laboratory, University of Chicago	RCV000500090	SCV000594666	benign	not specified	2018-04-26	criteria provided, single submitter	clinical testing
Invitae	RCV000524700	SCV000626270	benign	Fanconi anemia	2024-01-30	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000524700	SCV002534227	benign	Fanconi anemia	2020-02-26	criteria provided, single submitter	curation
Ambry Genetics	RCV002392931	SCV002698771	uncertain significance	Inborn genetic diseases	2014-07-07	criteria provided, single submitter	clinical testing	The p.K498N variant (also known as c.1494G>T), located in coding exon 5 of the FANCB gene, results from a G to T substitution at nucleotide position 1494. The lysine at codon 498 is replaced by asparagine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs199510538, but a population frequency was unavailable. This variant was not reported in population based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6,500 samples with coverage at this position. This amino acid position is not conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence for this variant is limited at this time, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002488832	SCV002799993	likely benign	Fanconi anemia complementation group B; VACTERL association, X-linked, with or without hydrocephalus	2021-09-23	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000331306	SCV004017596	benign	Fanconi anemia complementation group B	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000500090	SCV001808069	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000500090	SCV001968244	benign	not specified		no assertion criteria provided	clinical testing