Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • See Evidence submitted by expert panel for details.

Variant: NM_206933.2(USH2A):c.11241C>A (p.Tyr3747Ter)

CA1393780

506273 (ClinVar)

Gene: USH2A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: b7a55bd1-1f82-499f-acdf-a7a6884c636c
Approved on: 2018-09-17
Published on: 2019-07-17

HGVS expressions

NM_206933.2:c.11241C>A
NM_206933.2(USH2A):c.11241C>A (p.Tyr3747Ter)
NC_000001.11:g.215758743G>T
CM000663.2:g.215758743G>T
NC_000001.10:g.215932085G>T
CM000663.1:g.215932085G>T
NC_000001.9:g.213998708G>T
NG_009497.1:g.669654C>A
NM_206933.3:c.11241C>A
ENST00000307340.7:c.11241C>A
More

Pathogenic

Met criteria codes 3
PM2_Supporting PVS1 PM3_Supporting
Not Met criteria codes 20
BP7 BP5 BP4 BP3 BP2 PM6 PM5 PM4 PM1 PS1 PS3 PS4 PS2 BA1 PP3 PP1 PP4 BS2 BS1 BS4

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The p.Tyr3747X variant in USH2A is predicted to cause a premature stop codon in biologically-relevant-exon 58/72 that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism (PVS1). The allele frequency of the p.Tyr3747X variant in the Ush2A gene is 0.017% (4/24020) of African chromosomes by the Genome Aggregation Database (http://gnomad.broadinstitute.org), 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 hearing loss ( PM2_Supporting). This variant has been detected in 1 patient with hearing loss in trans with a suspected pathogenic variant (PM3_Supporting, Partners LMM internal data SCV000713838.1). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied: PVS1, PM2_Supporting, PM3_Supporting.
Met criteria codes
PM2_Supporting
4/24020 (0.00017) in Africans in gnomAD. Meets PM2_P
PVS1
Predicted to undergo NMD (Exon 58/72 exons), exon is not alternately spliced
PM3_Supporting
Patient also has exon 63-64 deletion, phase not confirmed, but 63-64 del has been reported with other truncating variants (LMM internal data)
Not Met criteria codes
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
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
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
4/24020 (0.00017) in Africans in gnomAD. Meets PM2_P
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
4/24020 (0.00017) in Africans in gnomAD. Meets PM2_P
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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