Submissions for variant NM_000441.2(SLC26A4):c.1804-6G>A

gnomAD frequency: 0.00016  dbSNP: rs377713770

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000779526	SCV000916173	uncertain significance	SLC26A4-Related Disorders	2017-09-08	criteria provided, single submitter	clinical testing	The SLC26A4 c.1804-6G>A variant has been reported in at least 12 individuals with nonsyndromic hearing loss (Yang et al. 2005; Chen et al. 2011; Nishio & Usami 2015; Jiang et al. 2015; Wu et al. 2017). In three individuals with severe-to-profound hearing impairment, the variant was detected in trans with an intron variant (Wu et al. 2017), while in eight individuals, a second variant in the SLC26A4 gene was not identified. One of the heterozygous patients displayed severe prelingual hearing loss as well as bilateral enlarged vestibular aqueduct and Mondini dysplasia without goiter, but the patient was too young to conclude whether the variant predisposes to thyroid abnormalities (Yang et al. 2005). The c.1804-6G>A variant was absent from 319 normal hearing control individuals and is reported at a frequency of 0.003504 in the East Asian population of the Exome Aggregation Consortium. Functional studies of the variant have not been reported, but RT-PCR analysis of mRNA isolated from peripheral blood lymphocytes from a heterozygous individual did not indicate an effect on splicing (Yang et al. 2005). The evidence for this variant is limited. The c.1804-6G>A variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for SLC26A4-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae	RCV000937129	SCV001082904	benign	not provided	2024-01-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000937129	SCV001748223	uncertain significance	not provided	2021-06-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000937129	SCV001767568	likely benign	not provided	2020-09-25	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31980526, 21704276, 15574297, 30842343)