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NM_000441.2(SLC26A4):c.1001+1G>A AND Rare genetic deafness

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 13, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000824768.4

Allele description [Variation Report for NM_000441.2(SLC26A4):c.1001+1G>A]

NM_000441.2(SLC26A4):c.1001+1G>A

Gene:
SLC26A4:solute carrier family 26 member 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q22.3
Genomic location:
Preferred name:
NM_000441.2(SLC26A4):c.1001+1G>A
HGVS:
  • NC_000007.14:g.107683538G>A
  • NG_008489.1:g.27904G>A
  • NM_000441.2:c.1001+1G>AMANE SELECT
  • NC_000007.13:g.107323983G>A
  • NM_000441.1:c.1001+1G>A
  • c.1001+1G>A
Nucleotide change:
IVS8, G-A, +1
Links:
OMIM: 605646.0007; dbSNP: rs80338849
NCBI 1000 Genomes Browser:
rs80338849
Molecular consequence:
  • NM_000441.2:c.1001+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
17

Condition(s)

Name:
Rare genetic deafness
Identifiers:
MedGen: C5680250; Orphanet: 96210

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000060073Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Pathogenic
(Apr 13, 2017) 		germlineclinical testing

PubMed (11)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided2017not providednot providednot providedclinical testing

Citations

PubMed

SLC26A4/PDS genotype-phenotype correlation in hearing loss with enlargement of the vestibular aqueduct (EVA): evidence that Pendred syndrome and non-syndromic EVA are distinct clinical and genetic entities.

Pryor SP, Madeo AC, Reynolds JC, Sarlis NJ, Arnos KS, Nance WE, Yang Y, Zalewski CK, Brewer CC, Butman JA, Griffith AJ.

J Med Genet. 2005 Feb;42(2):159-65. No abstract available.

PubMed [citation]
PMID:
15689455
PMCID:
PMC1735974

Molecular analysis of the PDS gene in Pendred syndrome.

Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, Coffey R, Grueters A, Grossman4 A, Phelps PD, Luxon L, Kendall-Taylor P, Scherer SW, Trembath RC.

Hum Mol Genet. 1998 Jul;7(7):1105-12.

PubMed [citation]
PMID:
9618167
See all PubMed Citations (11)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060073.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided20not providednot providedclinical testing PubMed (11)

Description

The c.1001+1G>A variant in SLC26A4 has been previously described in the literatu re in individuals with Pendred syndrome/DFNB4 with well-established pathogenicit y (Coyle 1998, Campbell 2001, Bogazzi 2000, Lopez-Bigas 2001, Fugazzola 2002, Ts ukamoto 2003, Bogazzi 2004, Pryor 2005, Madden 2007, Pera 2008, Pourova 2010). T his variant is present in 47/125744 European chromosomes by the Genome Aggregati on Database; however, this frequency is low enough to be consistent with a carri er frequency for recessive hearing loss or Pendred syndrome (gnomAD, http://gnom ad.broadinstitute.org; dbSNP rs80338849). This variant occurs in the invariant r egion (+/- 1,2) of the splice consensus sequence and is predicted to cause alter ed splicing leading to an abnormal or absent protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive DFNB4/Pend red syndrome based on the previously reported biallelic occurrences in affected individuals, association with specific clinical features, a low frequency in the general population, and predicted impact to the protein. ACMG/AMP criteria appl ied: PVS1, PS4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided20not provided17not provided

Last Updated: Oct 26, 2024