rs796051866

Positions:

• chr5-90642651-CCAAGTGCTGAAAT-C

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_032119.4(ADGRV1):​c.2258_2270delAAGTGCTGAAATC​(p.Gln753fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADGRV1 NM_032119.4 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 8.96

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]

ADGRV1 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 18 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 5-90642651-CCAAGTGCTGAAAT-C is Pathogenic according to our data. Variant chr5-90642651-CCAAGTGCTGAAAT-C is described in ClinVar as [Pathogenic]. Clinvar id is 6804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90642651-CCAAGTGCTGAAAT-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4	c.2258_2270delAAGTGCTGAAATC	p.Gln753fs	frameshift_variant	12/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9	c.2258_2270delAAGTGCTGAAATC	p.Gln753fs	frameshift_variant	12/90	1	NM_032119.4	ENSP00000384582.2
ADGRV1	ENST00000640403	c.-440_-428delAAGTGCTGAAATC		5_prime_UTR_variant	2/29	5		ENSP00000492531.1
ADGRV1	ENST00000504142.2	n.1024_1036delAAGTGCTGAAATC		non_coding_transcript_exon_variant	6/14	5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Usher syndrome type 2C Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2009

- -

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

GeneDx

Oct 01, 2024

Frameshift variant predicted to result in protein truncation or 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: 19357117, 21569298) -

Retinal dystrophy Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs796051866; hg19: chr5-89938468;