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

CA10576905

228282 (ClinVar)

Gene: MYO7A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
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
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Likely Pathogenic

Met criteria codes 4
PM3 PM2 PP3 PP4

Evidence Links 1

Expert Panel

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.
Met criteria codes
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).

PM2
This variant was absent from both versions of gnomAD.
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.
Curation History
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