NM_032119.4(ADGRV1):c.4264A>G (p.Ser1422Gly) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Oct 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000826329.3

Allele description [Variation Report for NM_032119.4(ADGRV1):c.4264A>G (p.Ser1422Gly)]

NM_032119.4(ADGRV1):c.4264A>G (p.Ser1422Gly)

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.4264A>G (p.Ser1422Gly)
HGVS:
  • NC_000005.10:g.90653838A>G
  • NG_007083.2:g.129495A>G
  • NM_032119.4:c.4264A>GMANE SELECT
  • NP_115495.3:p.Ser1422Gly
  • LRG_1095t1:c.4264A>G
  • LRG_1095:g.129495A>G
  • LRG_1095p1:p.Ser1422Gly
  • NC_000005.9:g.89949655A>G
  • NM_032119.3:c.4264A>G
  • NR_003149.2:n.4363A>G
Protein change:
S1422G
Links:
dbSNP: rs377136573
NCBI 1000 Genomes Browser:
rs377136573
Molecular consequence:
  • NM_032119.4:c.4264A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_003149.2:n.4363A>G - 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
SCV000967913GeneDxcriteria provided, single submitter
Likely benign
(May 12, 2018)
germlineclinical testing

Citation Link,

SCV001384515Invitaecriteria provided, single submitter
Uncertain significance
(Oct 8, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From GeneDx, SCV000967913.1

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Invitae, SCV001384515.2

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

Description

This sequence change replaces serine with glycine at codon 1422 of the ADGRV1 protein (p.Ser1422Gly). The serine residue is weakly conserved and there is a small physicochemical difference between serine and glycine. This variant is present in population databases (rs377136573, ExAC 0.2%). This variant has not been reported in the literature in individuals with ADGRV1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Mar 14, 2021

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