5-90692687-A-T

Variant summary

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

The NM_032119.4(ADGRV1):​c.7034A>T​(p.Asn2345Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N2345S) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

9
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.06
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]

Genome browser will be placed here

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, 0.832

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADGRV1NM_032119.4 linkuse as main transcriptc.7034A>T p.Asn2345Ile missense_variant 32/90 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.7034A>T p.Asn2345Ile missense_variant 32/901 NM_032119.4 ENSP00000384582.2 Q8WXG9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457634
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
724696
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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), LabcorpMay 19, 2022This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 2345 of the ADGRV1 protein (p.Asn2345Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ADGRV1-related conditions. 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
0.87
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
D;D;.
Eigen
Pathogenic
0.97
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
.;D;D
M_CAP
Pathogenic
0.36
D
MetaRNN
Pathogenic
0.83
D;D;D
MetaSVM
Benign
-0.31
T
PrimateAI
Uncertain
0.49
T
PROVEAN
Pathogenic
-7.9
.;D;.
REVEL
Uncertain
0.60
Sift
Pathogenic
0.0
.;D;.
Sift4G
Pathogenic
0.0
.;D;.
Polyphen
1.0
D;D;.
Vest4
0.89
MutPred
0.44
Loss of phosphorylation at Y2349 (P = 0.0884);Loss of phosphorylation at Y2349 (P = 0.0884);.;
MVP
0.76
MPC
0.35
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.93
gMVP
0.80

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs2366926; hg19: chr5-89988504; API