Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_194323.3:c.-27-1G>C

CA346124255

Gene: OTOF

Condition: autosomal recessive nonsyndromic deafness 9

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 81b3c3af-6394-49b6-bdc0-45693a69c89f

HGVS expressions

NM_194323.3:c.-27-1G>C

NC_000002.12:g.26477750C>G

CM000664.2:g.26477750C>G

NC_000002.11:g.26700618C>G

CM000664.1:g.26700618C>G

NC_000002.10:g.26554122C>G

NG_009937.1:g.85949G>C

ENST00000272371.7:c.2215-1G>C

ENST00000339598.8:c.-27-1G>C

ENST00000402415.8:c.-28G>C

ENST00000272371.6:c.2215-1G>C

ENST00000338581.10:c.-27-1G>C

ENST00000339598.7:c.-27-1G>C

ENST00000402415.7:c.144G>C

ENST00000403946.7:c.2215-1G>C

NM_001287489.1:c.2215-1G>C

NM_004802.3:c.-27-1G>C

NM_194248.2:c.2215-1G>C

NM_194322.2:c.144G>C

NM_194323.2:c.-27-1G>C

NM_001287489.2:c.2215-1G>C

NM_004802.4:c.-27-1G>C

NM_194248.3:c.2215-1G>C

NM_194322.3:c.144G>C

Likely Pathogenic

The Expert Panel has overridden the computationally generated classification - "Uncertain Significance - Insufficient Evidence"

PM2_Supporting PVS1

Evidence Links 0

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for OTOF and MYO15A Version 1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.2215-1G>C variant in OTOF occurs within the canonical splice acceptor site (-1) of intron 18. It is predicted to cause skipping of biologically-relevant-exon 19 of 47, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive nonsyndromic deafness based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PVS1 and PM2_P (ClinGen Hearing Loss VCEP specifications version 2; 7/21/2022).

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PVS1

It is predicted to cause skipping of biologically-relevant-exon 19 of 47, resulting in a frameshift leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).

Approved on: 2022-07-21

Published on: 2022-09-26

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