Submissions for variant NM_000441.2(SLC26A4):c.1707+5G>A

gnomAD frequency: 0.00001  dbSNP: rs192366176

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Division of Hearing and Balance Research, National Hospital Organization Tokyo Medical Center	RCV000515708	SCV000611820	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2017-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000657917	SCV000779684	pathogenic	not provided	2018-05-08	criteria provided, single submitter	clinical testing	The c.1707+5 G>A splice site variant in the SLC26A4 gene has been previously reported in both the homozygous and compound heterozygous state in association with SLC26A4-related disorders (Ganaha et al., 2013; Hao et al., 2018; Yang et al., 2005). The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This pathogenic variant destroys the natural splice donor site in intron 15, and is expected to cause abnormal gene splicing. In summary, we consider this to be a pathogenic variant.
Counsyl	RCV000669310	SCV000794052	pathogenic	Pendred syndrome	2017-09-07	criteria provided, single submitter	clinical testing
Invitae	RCV000657917	SCV000964527	pathogenic	not provided	2023-11-18	criteria provided, single submitter	clinical testing	This sequence change falls in intron 15 of the SLC26A4 gene. It does not directly change the encoded amino acid sequence of the SLC26A4 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs192366176, gnomAD 0.006%). This variant has been observed in individuals with Pendred syndrome or sensorineural hearing loss and enlarged vestibular aqueduct (PMID: 21961810, 23705809, 26763877). This variant is also known as IVS15+5G>A. ClinVar contains an entry for this variant (Variation ID: 446457). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000515708	SCV004201851	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2023-09-28	criteria provided, single submitter	clinical testing
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV000515708	SCV000902357	pathogenic	Autosomal recessive nonsyndromic hearing loss 4	2019-02-26	no assertion criteria provided	case-control
National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center	RCV000515708	SCV000994912	affects	Autosomal recessive nonsyndromic hearing loss 4	2019-08-20	no assertion criteria provided	clinical testing	in vitro experiment
Natera, Inc.	RCV000669310	SCV002080007	pathogenic	Pendred syndrome	2021-01-05	no assertion criteria provided	clinical testing