The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000260.4(MYO7A):c.5804T>C (p.Leu1935Pro)

CA278691

43298 (ClinVar)

Gene: MYO7A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
UUID: 1f484128-351e-49bd-a7a1-877c462ffac6
Approved on: 2024-09-24
Published on: 2024-09-27

HGVS expressions

NM_000260.4:c.5804T>C
NM_000260.4(MYO7A):c.5804T>C (p.Leu1935Pro)
NC_000011.10:g.77207350T>C
CM000673.2:g.77207350T>C
NC_000011.9:g.76918395T>C
CM000673.1:g.76918395T>C
NC_000011.8:g.76596043T>C
NG_009086.1:g.84086T>C
NG_009086.2:g.84105T>C
ENST00000409709.9:c.5804T>C
ENST00000670577.1:c.3631T>C
ENST00000409619.6:c.5657T>C
ENST00000409709.7:c.5804T>C
ENST00000458169.2:c.3230T>C
ENST00000458637.6:c.5690T>C
ENST00000481328.7:n.3340T>C
ENST00000605744.1:n.718T>C
NM_000260.3:c.5804T>C
NM_001127180.1:c.5690T>C
NM_001127180.2:c.5690T>C
NM_001369365.1:c.5657T>C
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Likely Pathogenic

Met criteria codes 4
PM3_Strong PM2_Supporting PP4 PP3
Not Met criteria codes 3
BS1 BP4 BA1

Evidence Links 0

Expert Panel

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.5804T>C variant in MYO7A is a missense variant predicted to cause substitution of leucine by proline at amino acid 1935 (p.Leu1935Pro). The highest population minor allele frequency in gnomAD v4.1 is 0.00002204 (26/1179460 alleles) in the European (non-Finnish) population, which is lower than the ClinGen Hearing Loss VCEP threshold (≤0.00007) for PM2_Supporting, meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.961, which is above the threshold of 0.7, evidence that correlates with impact to MYO7A function (PP3). This variant has been detected in 2 individuals with autosomal recessive Usher syndrome. Both were compound heterozygous for the variant and a pathogenic or likely pathogenic variant and both of those were confirmed in trans by family testing (2 PM3 points, SCV001239772.1, SCV000059855.6, Blueprint Genetics, Laboratory for Molecular Medicine) (PM3_Strong). At least one patient with this variant displayed sensorineural hearing loss with retinitis pigmentosa, which is highly specific for autosomal recessive Usher syndrome (PP4, SCV000059855.6, Laboratory for Molecular Medicine). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PM3_Strong, PM2_Supporting, PP3, PP4. (ClinGen Hearing Loss VCEP specifications version 2; 9/24/2024)
Met criteria codes
PM3_Strong
This variant has been detected in 2 individuals with Usher syndrome. Of those individuals, both were compound heterozygous for the variant and a pathogenic or likely pathogenic variant and both of those were confirmed in trans by family testing (2 PM3 points, PMIDs, Laboratory for Molecular Medicine, Blueprint Genetics, SCV000059855.6, SCV001239772.1)(PM3_Strong).
PM2_Supporting
The highest population minor allele frequency in gnomAD v4.1 is 0.00002204 (26/1179460 alleles) in the European (non-Finnish) population, which is lower than the ClinGen Hearing Loss VCEP threshold (≤0.00007) for PM2_Supporting, meeting this criterion (PM2_Supporting).
PP4
At least one patient with this variant displayed hearing loss and retinitis pigmentosa, which is highly specific for Usher syndrome (PP4, PMIDs, Laboratory for Molecular Medicine, Blueprint Genetics, SCV000059855.6, SCV001239772.1).
PP3
The computational predictor REVEL gives a score of 0.961, which is above the threshold of 0.7, evidence that correlates with impact to MYO7A function (PP3).
Not Met criteria codes
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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