chr5-91153323-GGATATGGCCAGGGGTCACT-G
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_032119.4(ADGRV1):βc.18732_18750delβ(p.Tyr6244Ter) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000992 in 1,612,654 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.000033 ( 0 hom., cov: 32)
Exomes π: 0.0000075 ( 0 hom. )
Consequence
ADGRV1
NM_032119.4 frameshift
NM_032119.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.02
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]
LUCAT1 (HGNC:48498): (lung cancer associated transcript 1)
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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 5-91153323-GGATATGGCCAGGGGTCACT-G is Pathogenic according to our data. Variant chr5-91153323-GGATATGGCCAGGGGTCACT-G is described in ClinVar as [Pathogenic]. Clinvar id is 6801.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-91153323-GGATATGGCCAGGGGTCACT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.18732_18750del | p.Tyr6244Ter | frameshift_variant | 89/90 | ENST00000405460.9 | |
LOC107986432 | XR_001742795.2 | n.1208-1154_1208-1136del | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.18732_18750del | p.Tyr6244Ter | frameshift_variant | 89/90 | 1 | NM_032119.4 | P1 | |
LUCAT1 | ENST00000650150.1 | n.380-1154_380-1136del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000810 AC: 2AN: 247032Hom.: 0 AF XY: 0.00000746 AC XY: 1AN XY: 134010
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GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460452Hom.: 0 AF XY: 0.00000551 AC XY: 4AN XY: 726372
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74356
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Usher syndrome type 2C Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2004 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change creates a premature translational stop signal (p.Tyr6244*) 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 (rs761560344, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 14740321). ClinVar contains an entry for this variant (Variation ID: 6801). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at