Submissions for variant NM_006005.3(WFS1):c.2477G>A (p.Ser826Asn)

dbSNP: rs1730968028

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV003147621	SCV003804397	likely risk allele	Wolfram syndrome 1		criteria provided, single submitter	research	Potent mutations in WFS1 gene are associated with Wolfram's syndrome, an autosomal recessive condition, which cause diabetes mellitus, diabetes insipidus, deafness and optic atrophy. However no sufficient evidence is found to ascertain the role of this particular variant rs1730968028 in Wolfram's syndrome yet.
HUSP Clinical Genetics Laboratory, Hospital Universitario San Pedro De Logroño (HUSP)	RCV001352903	SCV001547492	pathogenic	Autosomal dominant nonsyndromic hearing loss 6	2019-05-14	no assertion criteria provided	clinical testing	The c.2477 G>A variant, located in coding exon 8 of the WFS1 gene (NM_006005.3), results from a G to A substitution at nucleotide position 2477. The serine at codon 826 is replaced by asparagine (p.Ser826Asn). This alteration has not been reported previously in the literature and it is not detected in general population. In-silico tools predict that it is very likely to affect protein function. Heterozygous pathological variants in the WFS1 gene are associated with the phenotype of Deafness autosomal dominant 6 (OMIM: 600965). The c.2477 G>A variant was detected in a 4-year-old girl who suffered bilateral deafness. The variant was detected in her maternal grandfather, maternal uncle and her mother (all of them with hearing loss). Therefore, we consider that clinical significance of c.2477 G>A variant is pathogenic.