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

CA6197659

556881 (ClinVar)

Gene: MYO7A

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

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

• Met criteria codes: PM2_Supporting PP3

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

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.

Met criteria codes

• 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
• PP3: REVEL 0.841