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.14276G>A (p.Gly4759Glu)

CA180987

177913 (ClinVar)

Gene: USH2A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 1310f3c8-c6e5-4dda-9bc7-535ace6a44e0
Approved on: 2019-05-14
Published on: 2019-10-18

HGVS expressions

NM_206933.2:c.14276G>A
NM_206933.2(USH2A):c.14276G>A (p.Gly4759Glu)
NC_000001.11:g.215650659C>T
CM000663.2:g.215650659C>T
NC_000001.10:g.215824001C>T
CM000663.1:g.215824001C>T
NC_000001.9:g.213890624C>T
NG_009497.1:g.777738G>A
NM_206933.3:c.14276G>A
ENST00000307340.7:c.14276G>A
More

Likely Benign

Met criteria codes 2
BS1 BP4
Not Met criteria codes 21
PM3 PM1 PM5 PM4 PM2 PM6 BS2 BS4 BP7 BP5 BP2 BP3 PVS1 PS4 PS2 PS3 PS1 BA1 PP1 PP4 PP3

Evidence Links 1

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.14276G>A (p.Gly4759Glu) variant has been detected in at least 4 heterozygous individuals with clinical features of hearing loss or retinitis pigmentosa (PS4/PM3 not met; Partners LMM internal data, PMID 28041643). However, the filtering allele frequency (the lower threshold of the 95% CI of 102/24022) of the p.Gly4759Glu variant in the USH2A gene is 0.425% for African chromosomes by gnomAD, which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1).
Met criteria codes
BS1
Variant has been observed in 102/24022 (0.425%) African alleles in gnomAD
BP4
REVEL score is 0.111
Not Met criteria codes
PM3
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
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
PM2
Variant has been observed in 102/24022 (0.425%) African alleles in gnomAD
PM6
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
Patient has 4 variants in USH2A with RP and the case is considered "partially solved" but none of these variants are considered LP or P so this cannot be used.
Patient G005232: Patient has RP, African male. Patient has 4 variants in USH2A USH2A p.Gly4759Glu (VUS/LB) USH2A p.Pro4232Gln (VUS) USH2A p.Leu2962Ile (VUS) USH2A p.Gln2951Glu (VUS) PubMed:28041643
BP2
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
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
LMM: 3 patients with variable onset, severity of HL and syndromic features were het for the p.Gly4759Glu variant in USH2A and did not carry any other USH2A variants. No patients had RP reported. Carss 2017: Patient has 4 USH2A variants, can't count this as a PM3 case but might use this variant as a case-control.
Patient G005232: Patient has RP, African male. Patient has 4 variants in USH2A USH2A p.Gly4759Glu (VUS/LB) USH2A p.Pro4232Gln (VUS) USH2A p.Leu2962Ile (VUS) USH2A p.Gln2951Glu (VUS) PubMed:28041643
PS2
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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
Variant has been observed in 102/24022 (0.425%) African alleles in gnomAD
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
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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