NM_032119.4(ADGRV1):c.8651T>C (p.Val2884Ala) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Jul 19, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000039651.4

Allele description [Variation Report for NM_032119.4(ADGRV1):c.8651T>C (p.Val2884Ala)]

NM_032119.4(ADGRV1):c.8651T>C (p.Val2884Ala)

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.8651T>C (p.Val2884Ala)
HGVS:
  • NC_000005.10:g.90706315T>C
  • NG_007083.2:g.181972T>C
  • NM_032119.4:c.8651T>CMANE SELECT
  • NP_115495.3:p.Val2884Ala
  • LRG_1095t1:c.8651T>C
  • LRG_1095:g.181972T>C
  • LRG_1095p1:p.Val2884Ala
  • NC_000005.9:g.90002132T>C
  • NM_032119.3:c.8651T>C
  • NR_003149.2:n.8667T>C
  • c.8651T>C
Protein change:
V2884A
Links:
dbSNP: rs111033517
NCBI 1000 Genomes Browser:
rs111033517
Molecular consequence:
  • NM_032119.4:c.8651T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_003149.2:n.8667T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000063340Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely benign
(Feb 3, 2010)
germlineclinical testing

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

SCV000297335Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphiacriteria provided, single submitter
Uncertain significance
(Aug 10, 2015)
unknownclinical testing

DGD_Variant_Analysis_Guidelines.docx,

Citation Link,

SCV001774676Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jul 19, 2021)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss.

Sloan-Heggen CM, Bierer AO, Shearer AE, Kolbe DL, Nishimura CJ, Frees KL, Ephraim SS, Shibata SB, Booth KT, Campbell CA, Ranum PT, Weaver AE, Black-Ziegelbein EA, Wang D, Azaiez H, Smith RJH.

Hum Genet. 2016 Apr;135(4):441-450. doi: 10.1007/s00439-016-1648-8. Epub 2016 Mar 11.

PubMed [citation]
PMID:
26969326
PMCID:
PMC4796320

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000063340.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia, SCV000297335.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001774676.1

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

Description

Variant summary: ADGRV1 c.8651T>C (p.Val2884Ala) results in a non-conservative amino acid change located in the Na-Ca exchanger/integrin-beta4 domain (IPR003644) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 248472 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ADGRV1 causing Usher Syndrome (6e-05 vs 0.0054), allowing no conclusion about variant significance. c.8651T>C has been reported in the literature in at least one individual with a clinical diagnosis of Usher syndrome (Sloan-Heggen_2016). The data does not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Nov 27, 2021

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