NM_000441.2(SLC26A4):c.1707+5G>A AND not provided

Clinical significance:Pathogenic (Last evaluated: May 13, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1707+5G>A]


SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
Other names:
  • NC_000007.14:g.107700180G>A
  • NG_008489.1:g.44546G>A
  • NM_000441.2:c.1707+5G>AMANE SELECT
  • NC_000007.13:g.107340625G>A
  • NM_000441.1:c.1707+5G>A
dbSNP: rs192366176
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000441.2:c.1707+5G>A - intron variant - [Sequence Ontology: SO:0001627]
Functional consequence:
sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000779684GeneDxcriteria provided, single submitter
(May 8, 2018)
germlineclinical testing

Citation Link,

SCV000964527Invitaecriteria provided, single submitter
(May 13, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct.

Huang S, Han D, Yuan Y, Wang G, Kang D, Zhang X, Yan X, Meng X, Dong M, Dai P.

J Transl Med. 2011 Sep 30;9:167. doi: 10.1186/1479-5876-9-167.

PubMed [citation]

Pathogenic substitution of IVS15 + 5G > A in SLC26A4 in patients of Okinawa Islands with enlarged vestibular aqueduct syndrome or Pendred syndrome.

Ganaha A, Kaname T, Yanagi K, Naritomi K, Tono T, Usami S, Suzuki M.

BMC Med Genet. 2013 May 24;14:56. doi: 10.1186/1471-2350-14-56.

PubMed [citation]
See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000779684.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV000964527.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)


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, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs192366176, ExAC 0.02%). This variant has been observed in individuals affected with Pendred syndrome or sensorineural hearing loss and enlarged vestibular aqueduct (PMID: 21961810, 23705809, 26763877). This variant is also known as IVS15+5G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 446457). Nucleotide substitutions within 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, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2021

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