rs975296721

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_032119.4(ADGRV1):​c.8471G>A​(p.Gly2824Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ADGRV1
NM_032119.4 missense

Scores

11
6
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.39
Variant links:
Genes affected
ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADGRV1NM_032119.4 linkuse as main transcriptc.8471G>A p.Gly2824Glu missense_variant 37/90 ENST00000405460.9 NP_115495.3 Q8WXG9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADGRV1ENST00000405460.9 linkuse as main transcriptc.8471G>A p.Gly2824Glu missense_variant 37/901 NM_032119.4 ENSP00000384582.2 Q8WXG9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 13, 2021This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 2824 of the ADGRV1 protein (p.Gly2824Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Usher syndrome (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;D;.
Eigen
Pathogenic
1.0
Eigen_PC
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.87
.;D;D
M_CAP
Pathogenic
0.41
D
MetaRNN
Pathogenic
0.77
D;D;D
MetaSVM
Uncertain
-0.24
T
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-6.7
.;D;.
REVEL
Uncertain
0.46
Sift
Pathogenic
0.0
.;D;.
Sift4G
Pathogenic
0.0
.;D;.
Polyphen
1.0
D;D;.
Vest4
0.92
MutPred
0.32
Gain of disorder (P = 0.0363);Gain of disorder (P = 0.0363);.;
MVP
0.82
MPC
0.36
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.96
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs975296721; hg19: chr5-90001301; COSMIC: COSV67992132; API