NM_032119.4(ADGRV1):c.10426G>A (p.Gly3476Arg) AND Usher syndrome, type 2C

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Aug 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000454263.3

Allele description [Variation Report for NM_032119.4(ADGRV1):c.10426G>A (p.Gly3476Arg)]

NM_032119.4(ADGRV1):c.10426G>A (p.Gly3476Arg)

Gene:
ADGRV1:adhesion G protein-coupled receptor V1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q14.3
Genomic location:
Preferred name:
NM_032119.4(ADGRV1):c.10426G>A (p.Gly3476Arg)
Other names:
NM_032119.3:c.10426G>A, p.(Gly3476Arg)
HGVS:
  • NC_000005.10:g.90728933G>A
  • NG_007083.2:g.204590G>A
  • NM_032119.4:c.10426G>AMANE SELECT
  • NP_115495.3:p.Gly3476Arg
  • LRG_1095t1:c.10426G>A
  • LRG_1095:g.204590G>A
  • LRG_1095p1:p.Gly3476Arg
  • NC_000005.9:g.90024750G>A
  • NM_032119.3:c.10426G>A
  • NR_003149.2:n.10442G>A
Protein change:
G3476R
Links:
dbSNP: rs1060499795
NCBI 1000 Genomes Browser:
rs1060499795
Molecular consequence:
  • NM_032119.4:c.10426G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_003149.2:n.10442G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Usher syndrome, type 2C (USH2C)
Synonyms:
USHER SYNDROME, TYPE IIC; Usher syndrome, type 2B
Identifiers:
MONDO: MONDO:0011558; MedGen: C2931213; Orphanet: 231178; Orphanet: 886; OMIM: 605472

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000538092Hereditary Research Laboratory, Bethlehem Universityno assertion criteria providedPathogenic
(Jun 4, 2016)
germlineresearch

SCV001527130Baylor Geneticscriteria provided, single submitter
Uncertain significance
(Jun 22, 2018)
maternalclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001976379King Laboratory,University of Washingtoncriteria provided, single submitter
Likely pathogenic
(Aug 1, 2020)
germlineresearch

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedresearch
not providedmaternalyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Genomic analysis of inherited hearing loss in the Palestinian population.

Abu Rayyan A, Kamal L, Casadei S, Brownstein Z, Zahdeh F, Shahin H, Canavati C, Dweik D, Jaraysa T, Rabie G, Carlson RJ, Gulsuner S, Lee MK, Avraham KB, Walsh T, King MC, Kanaan MN.

Proc Natl Acad Sci U S A. 2020 Aug 18;117(33):20070-20076. doi: 10.1073/pnas.2009628117. Epub 2020 Aug 3.

PubMed [citation]
PMID:
32747562
PMCID:
PMC7443947

Details of each submission

From Hereditary Research Laboratory, Bethlehem University, SCV000538092.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearchnot provided

Description

congenital, moderate to severe

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

From Baylor Genetics, SCV001527130.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1maternalyesnot providednot providednot providednot providednot providednot providednot provided

From King Laboratory,University of Washington, SCV001976379.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)

Description

Analysis of patient-derived RNA indicates that ADGRV1 c.10426+1G>A disrupts the donor splice site of ADGRV1 exon 49, leading to transcriptional loss of 209bp and a premature stop (Abu Rayyan 2020). The variant is homozygous in 3 Palestinian children with moderate to severe hearing loss from 3 different families. The variant is absent from 1300 Palestinian controls and absent from public databases.

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

Last Updated: Oct 8, 2021

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