rs373780305
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_032119.4(ADGRV1):c.2398C>T(p.Arg800*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000023 in 1,607,408 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 Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_032119.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000329 AC: 8AN: 243508Hom.: 0 AF XY: 0.0000378 AC XY: 5AN XY: 132116
GnomAD4 exome AF: 0.0000234 AC: 34AN: 1455344Hom.: 0 Cov.: 33 AF XY: 0.0000249 AC XY: 18AN XY: 723578
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152064Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74280
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Nonsense variant predicted to result in nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22135276, 31589614) -
This sequence change creates a premature translational stop signal (p.Arg800*) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADGRV1 are known to be pathogenic (PMID: 19357117, 22135276, 22147658, 26226137, 30718709, 31047384, 32467589). This variant is present in population databases (rs373780305, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 22135276). ClinVar contains an entry for this variant (Variation ID: 46306). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. -
Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Pathogenic:1
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Rare genetic deafness Pathogenic:1
The Arg800X variant in GPR98 has been reported in one individual with Usher synd rome who had a second GPR98 variant (Le Quesne Stabej 2012). This nonsense varia nt leads to a premature termination codon at position 800, which is predicted to lead to a truncated or absent protein. In summary, this variant meets our crite ria to be classified as pathogenic (http://pcpgm.partners.org/LMM). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at