Variant 5-90118337-TTTTTGTGATGATGTTGTTTTTAGACATTGTATCTCTCTCTCTCTGTCATCCATGCCCTACACTTCAGTTAAAACACATGAGTAGCTAGTACCAAAATGTCCCACATCGTGCTGTACTTCTGTGTTGAAGCTTCTATTACTGTTTTTCAAAATCAAATTTCTTTGGGTCAGGCACAGTGGCTTATGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGCAGGCGGATCACAAGGTCAGGAGTTCAAGACCAACCTGGCCAACATAGTGAAACCCCATCTCTACTAAAAATACAAAAAAATTTGCTGGGCGTGGTGGTGGGTGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCACGAGAATTGCTTGAACCTAGGGGACGGAGTTTGGAGTGAGCCGAGATCACGCCACTGCACTCCAGCCCGGGCAATGGTGCGAGACTCCATCTCAAAAAAAAAAAAAAAAAGAAATCAAATTTCTTTGGAAATTAACAATTCATTAGGACAGGTTTGATGAAACCTGAAAGAAAGATTTCATGATTTTCTTAGGCAAAAAATTATCTAATGTAATTATATATATTATTAAAGTTAAAGATGATGGGGCTGGGTGGATGTGGGGAAGTAAGGGGAAAGTTGACTTGAATCACCAATGCAGAAGCCACTTTATACAACTATTATGAGCCATGAAATTATTTTTAAAAGCCACATGGAAACTTTTTTATTCTAAATGTATTTTTTCTGAATAATTCTTTCAGAAGCAATCAAGGTAAAAGACTTTGACTTTTGCATAACTATACTATAGGCAGTCACAGTGTATCAGTTTGACCTCACTGCTTTCTGAGCTGACAAGTCTCAGGCATTTGATGAAACCAATATCCACCCATGCCATAGAGTAGAACAATATTTAGACA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Consequence

Unknown

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 1.68

Variant links:

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ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-90118337-TTTTTGTGATGATGTTGTTTTTAGACATTGTATCTCTCTCTCTCTGTCATCCATGCCCTACACTTCAGTTAAAACACATGAGTAGCTAGTACCAAAATGTCCCACATCGTGCTGTACTTCTGTGTTGAAGCTTCTATTACTGTTTTTCAAAATCAAATTTCTTTGGGTCAGGCACAGTGGCTTATGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGCAGGCGGATCACAAGGTCAGGAGTTCAAGACCAACCTGGCCAACATAGTGAAACCCCATCTCTACTAAAAATACAAAAAAATTTGCTGGGCGTGGTGGTGGGTGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCACGAGAATTGCTTGAACCTAGGGGACGGAGTTTGGAGTGAGCCGAGATCACGCCACTGCACTCCAGCCCGGGCAATGGTGCGAGACTCCATCTCAAAAAAAAAAAAAAAAAGAAATCAAATTTCTTTGGAAATTAACAATTCATTAGGACAGGTTTGATGAAACCTGAAAGAAAGATTTCATGATTTTCTTAGGCAAAAAATTATCTAATGTAATTATATATATTATTAAAGTTAAAGATGATGGGGCTGGGTGGATGTGGGGAAGTAAGGGGAAAGTTGACTTGAATCACCAATGCAGAAGCCACTTTATACAACTATTATGAGCCATGAAATTATTTTTAAAAGCCACATGGAAACTTTTTTATTCTAAATGTATTTTTTCTGAATAATTCTTTCAGAAGCAATCAAGGTAAAAGACTTTGACTTTTGCATAACTATACTATAGGCAGTCACAGTGTATCAGTTTGACCTCACTGCTTTCTGAGCTGACAAGTCTCAGGCATTTGATGAAACCAATATCCACCCATGCCATAGAGTAGAACAATATTTAGACA-T is Pathogenic according to our data. Variant chr5-90118337-TTTTTGTGATGATGTTGTTTTTAGACATTGTATCTCTCTCTCTCTGTCATCCATGCCCTACACTTCAGTTAAAACACATGAGTAGCTAGTACCAAAATGTCCCACATCGTGCTGTACTTCTGTGTTGAAGCTTCTATTACTGTTTTTCAAAATCAAATTTCTTTGGGTCAGGCACAGTGGCTTATGCCTGTAATCCCAGCACTTTGGGAGGCCAAGGCAGGCGGATCACAAGGTCAGGAGTTCAAGACCAACCTGGCCAACATAGTGAAACCCCATCTCTACTAAAAATACAAAAAAATTTGCTGGGCGTGGTGGTGGGTGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCACGAGAATTGCTTGAACCTAGGGGACGGAGTTTGGAGTGAGCCGAGATCACGCCACTGCACTCCAGCCCGGGCAATGGTGCGAGACTCCATCTCAAAAAAAAAAAAAAAAAGAAATCAAATTTCTTTGGAAATTAACAATTCATTAGGACAGGTTTGATGAAACCTGAAAGAAAGATTTCATGATTTTCTTAGGCAAAAAATTATCTAATGTAATTATATATATTATTAAAGTTAAAGATGATGGGGCTGGGTGGATGTGGGGAAGTAAGGGGAAAGTTGACTTGAATCACCAATGCAGAAGCCACTTTATACAACTATTATGAGCCATGAAATTATTTTTAAAAGCCACATGGAAACTTTTTTATTCTAAATGTATTTTTTCTGAATAATTCTTTCAGAAGCAATCAAGGTAAAAGACTTTGACTTTTGCATAACTATACTATAGGCAGTCACAGTGTATCAGTTTGACCTCACTGCTTTCTGAGCTGACAAGTCTCAGGCATTTGATGAAACCAATATCCACCCATGCCATAGAGTAGAACAATATTTAGACA-T is described in ClinVar as [Pathogenic]. Clinvar id is 2445626.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Usher syndrome type 2C

Pathogenic:1

Pathogenic, criteria provided, single submitter

research

King Laboratory, University of Washington

Feb 28, 2023

This variant was found in homozygosity in two siblings with Usher Syndrome Type 2, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). These two patients were born to consanguineous parents and have a 1st cousin with a similar hearing loss. This variant is a chromosomal deletion that is predicted to alter splicing. The deletion includes the 5’ end of ADGRV1 exon 76, which is likely to lead to exon skipping, a frameshift in the coding sequence, and early truncation. As of January 2023, this variant has not been reported to ClinVar and is not found on gnomAD. Based on the prediction that this variant leads to a splicing error and a truncated protein, co-segregation with the phenotype in the family, and goodness of fit of genotype to phenotype, we conclude that this variant is pathogenic. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.