rs1554068885
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_032119.4(ADGRV1):c.2302G>T(p.Glu768Ter) variant causes a stop gained change. 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. E768E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Consequence
ADGRV1
NM_032119.4 stop_gained
NM_032119.4 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 6.28
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-90642697-G-T is Pathogenic according to our data. Variant chr5-90642697-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 504947.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.2302G>T | p.Glu768Ter | stop_gained | 12/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.2302G>T | p.Glu768Ter | stop_gained | 12/90 | 1 | NM_032119.4 | P1 | |
ADGRV1 | ENST00000640403.1 | c.-396G>T | 5_prime_UTR_variant | 2/29 | 5 | ||||
ADGRV1 | ENST00000504142.2 | n.1068G>T | non_coding_transcript_exon_variant | 6/14 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Rare genetic deafness Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 05, 2016 | The p.Glu768X variant in GPR98 has not been previously reported in individuals w ith hearing loss or Usher syndrome or in large population studies. This nonsense variant introduces a premature termination codon at position 768, which is pred icted to lead to a truncated or absent protein. Loss of GPR98 gene function is a known mechanism of autosomal recessive Usher syndrome. In summary, this variant meets criteria to be classified as pathogenic for Usher syndrome in an autosoma l recessive manner based upon the predicted impact to the protein and extremely low allele frequency in the general population. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
0.30
ClinPred
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at