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]

Variant: NM_000260.4(MYO7A):c.19G>A (p.Gly7Arg)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA6197006

802700 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bce470f8-6cff-46e7-813f-f8d6bc816152

Approved on: 2024-06-28

Published on: 2024-06-28

HGVS expressions

NM_000260.4:c.19G>A

NM_000260.4(MYO7A):c.19G>A (p.Gly7Arg)

NC_000011.10:g.77142709G>A

CM000673.2:g.77142709G>A

NC_000011.9:g.76853755G>A

CM000673.1:g.76853755G>A

NC_000011.8:g.76531403G>A

NG_009086.1:g.19446G>A

NG_009086.2:g.19464G>A

ENST00000409709.9:c.19G>A

ENST00000660626.1:c.109G>A

ENST00000409619.6:c.-15G>A

ENST00000409709.7:c.19G>A

ENST00000409893.5:c.19G>A

ENST00000458637.6:c.19G>A

ENST00000620575.4:c.19G>A

NM_000260.3:c.19G>A

NM_001127179.2:c.19G>A

NM_001127180.1:c.19G>A

NM_001127180.2:c.19G>A

NM_001369365.1:c.-15G>A

Uncertain Significance

BS1_Supporting PP3

PM3

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 CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2

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Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.19G>A (p.Gly7Arg) variant in MYO7A is a missense variant predicted to cause a substitution of glycine by arginine at amino acid 7. The filtering allele frequency (the lower threshold of the 95% CI of 95/74936) of the c.19G>A in MYO7A is 0.1061% for African/African American chromosomes by gnomAD v4.0.0, which is higher than the ClinGen Hearing Loss VCEP threshold (≥0.0007) for BS1_Supporting, and therefore meets this criterion (BS1_Supporting). Two probands were compound heterozygous with one confirmed trans with the pathogenic c.6377del, p.Pro2126Leufs*5 variant, and the other one assumed in trans with the pathogenic c.634C>T, p.Arg212Cys variant (ClinVar ID: 802700, internal data from Invitae). However, due to the allele frequency meeting BS1_Supporting criteria, PM3 was not applied. The computational predictor REVEL gives a score of 0.926 which is above the threshold of ≥ 0.7 (PP3). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Usher Syndrome Type 1, based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP (BS1_Supporting, PP3; Version 2; 4/17/24).

BS1_Supporting

The filtering allele frequency (the lower threshold of the 95% CI of 95/74936) of the c.19G>A in MYO7A is 0.1061% for African/African American chromosomes by gnomAD v4.0.0, which is higher than the ClinGen Hearing Loss VCEP threshold (≥0.0007) for BS1_Supporting, and therefore meets this criterion (BS1_Supporting).

PP3

The computational predictor REVEL gives a score of 0.926 which is above the threshold of ≥ 0.7 (PP3).

PM3

Two probands were compound heterozygous with one confirmed trans with the pathogenic c.6377del, p.Pro2126Leufs*5 variant, and the other one assumed in trans with the pathogenic c.634C>T, p.Arg212Cys variant (ClinVar ID: 802700, internal data from Invitae). However, due to the allele frequency meeting BS1_Supporting criteria, PM3 was not applied.

Curation History

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