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.1997G>A (p.Arg666Gln)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA6197659

556881 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4923dcaa-6018-41a1-b68f-39af89d9e3cf

Approved on: 2020-05-20

Published on: 2020-05-20

HGVS expressions

NM_000260.4:c.1997G>A

NM_000260.4(MYO7A):c.1997G>A (p.Arg666Gln)

NC_000011.10:g.77174817G>A

CM000673.2:g.77174817G>A

NC_000011.9:g.76885863G>A

CM000673.1:g.76885863G>A

NC_000011.8:g.76563511G>A

NG_009086.1:g.51554G>A

NG_009086.2:g.51572G>A

NM_000260.3:c.1997G>A

NM_001127179.2:c.1997G>A

NM_001127180.1:c.1997G>A

NM_001127180.2:c.1997G>A

NM_001369365.1:c.1964G>A

ENST00000409619.6:c.1964G>A

ENST00000409709.7:c.1997G>A

ENST00000409893.5:c.1997G>A

ENST00000458637.6:c.1997G>A

ENST00000620575.4:c.1997G>A

Uncertain Significance

PP3 PM2_Supporting

Evidence Links 0

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.1997G>A (p.Arg666Gln) variant in MYO7A is present in 10/42046 (0.012% CI 95%) of African alleles in gnomAD v3, which is a low enough frequency to award PM2_Supporting based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive Usher syndrome (PM2_Supporting). This variant has been detected in 1 proband with Usher syndrome, however, they carried another VUS with phase unknown (PM3_Supporting not met; ClinVar ID: 196099; PMIDs: 27460420, 31479088). The REVEL computational prediction analysis tool produced a score of 0.841, which is above the threshold necessary to apply PP3. In summary, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2_Supporting, PP3.

PP3

REVEL 0.841

PM2_Supporting

3/23890 (0.00034% CI 95%) African alleles in gnomAD v2.1.1 10/42046 (0.0129% CI 95%) African alleles in gnomAD v3

Curation History

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