NM_032119.4(ADGRV1):c.5967dup (p.Val1990fs) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 27, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001009156.3

Allele description [Variation Report for NM_032119.4(ADGRV1):c.5967dup (p.Val1990fs)]

NM_032119.4(ADGRV1):c.5967dup (p.Val1990fs)

Gene:
ADGRV1:adhesion G protein-coupled receptor V1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
5q14.3
Genomic location:
Preferred name:
NM_032119.4(ADGRV1):c.5967dup (p.Val1990fs)
HGVS:
  • NC_000005.10:g.90683888dup
  • NG_007083.2:g.159545dup
  • NM_032119.4:c.5967dupMANE SELECT
  • NP_115495.3:p.Val1990fs
  • LRG_1095t1:c.5967dup
  • LRG_1095:g.159545dup
  • LRG_1095p1:p.Val1990fs
  • NC_000005.9:g.89979702_89979703insA
  • NC_000005.9:g.89979705dup
  • NM_032119.3:c.5967dup
  • NM_032119.3:c.5967dupA
  • NR_003149.2:n.6066dup
Protein change:
V1990fs
Links:
dbSNP: rs778288846
NCBI 1000 Genomes Browser:
rs778288846
Molecular consequence:
  • NM_032119.4:c.5967dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_003149.2:n.6066dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001168972GeneDxcriteria provided, single submitter
Likely pathogenic
(Dec 18, 2018)
germlineclinical testing

Citation Link,

SCV001199946Invitaecriteria provided, single submitter
Pathogenic
(Mar 27, 2020)
germlineclinical testing

PubMed (4)
[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

Citations

PubMed

GPR98 mutations cause Usher syndrome type 2 in males.

Ebermann I, Wiesen MH, Zrenner E, Lopez I, Pigeon R, Kohl S, Löwenheim H, Koenekoop RK, Bolz HJ.

J Med Genet. 2009 Apr;46(4):277-80. doi: 10.1136/jmg.2008.059626.

PubMed [citation]
PMID:
19357117

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

Le Quesne Stabej P, Saihan Z, Rangesh N, Steele-Stallard HB, Ambrose J, Coffey A, Emmerson J, Haralambous E, Hughes Y, Steel KP, Luxon LM, Webster AR, Bitner-Glindzicz M.

J Med Genet. 2012 Jan;49(1):27-36. doi: 10.1136/jmedgenet-2011-100468. Epub 2011 Dec 1.

PubMed [citation]
PMID:
22135276
PMCID:
PMC3678402
See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV001168972.1

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

Description

The c.5967dupA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). It causes a frameshift starting with codon Valine 1990, changes this amino acid to a Serine residue and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Val1990SerfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We consider this variant to be likely pathogenic.

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

From Invitae, SCV001199946.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Val1990Serfs*2) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs778288846, ExAC 0.003%). This variant has been observed in individual(s) with clinical features of Usher syndrome (Invitae). Loss-of-function variants in ADGRV1 are known to be pathogenic (PMID: 19357117, 22135276, 22147658). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 10, 2021

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