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.6062A>G (p.Lys2021Arg)

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CA10576905

228282 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: c7b98a09-bc39-416b-af89-f1dfff058317

Approved on: 2020-03-18

Published on: 2020-03-18

HGVS expressions

NM_000260.4:c.6062A>G

NM_000260.4(MYO7A):c.6062A>G (p.Lys2021Arg)

NC_000011.10:g.77211162A>G

CM000673.2:g.77211162A>G

NC_000011.9:g.76922207A>G

CM000673.1:g.76922207A>G

NC_000011.8:g.76599855A>G

NG_009086.1:g.87898A>G

NG_009086.2:g.87917A>G

ENST00000409709.9:c.6062A>G

ENST00000670577.1:c.3863A>G

ENST00000409619.6:c.5915A>G

ENST00000409709.7:c.6062A>G

ENST00000458169.2:c.3488A>G

ENST00000458637.6:c.5948A>G

ENST00000481328.7:n.3598A>G

ENST00000526863.2:n.25+251A>G

ENST00000605744.1:n.1529A>G

NM_000260.3:c.6062A>G

NM_001127180.1:c.5948A>G

NM_001127180.2:c.5948A>G

NM_001369365.1:c.5915A>G

Likely Pathogenic

PP3 PP4 PM2 PM3

Evidence Links 1

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The c.6062A>G (p.Lys2021Arg) variant in MYO7A was observed in at least 2 probands with Usher syndrome and a second pathogenic or likely pathogenic variant observed in the gene (PM3; PMID: 21436283; LMM internal data, SCV000271250.2). At least one of these individuals presented with hearing loss and retinitis pigmentosa, features highly specific for Usher syndrome (PP4). This variant was absent from large population databases (PM2; gnomad.broadinstitute.org). The REVEL computational prediction analysis tool produced a score of 0.75, which is above the threshold necessary to apply PP3. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: PM2, PM3, PP3, PP4.

PP3

REVEL score 0.748. Conserved in UCSC database, except for 1 mammal (elephant) which has Thr at this site. Alamut suggests that this variant may add a cryptic 5' splice site.

PP4

Proband from Roux et al. had audiology and fundus examination and/or electroretinogram. A diagnosis was made based on congenital profound SNHL, vestibular dysfunction, and retinal degeneration.

PM2

This variant was absent from both versions of gnomAD.

PM3

This variant was reported 1 proband (Roux et al. 2011, PMID: 21436283) diagnosed with Usher syndrome type I. French individual, compound het with c.722G>A (p.Arg241His), LP in ClinVar (Ambry, LMM), phase unknown. At LMM, it was seen in 1 proband with profound hearing loss and balance problems. The other variant found in MYO7A was c.2283-1G>T (skips exon 20), pathogenic, phase unknown (SCV000271250.2).

PubMed:21436283

Curation History

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