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]
  • Gene label mismatch: USH2A vs undefined
  • 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_206933.2(USH2A):c.5039A>G (p.Lys1680Arg)

CA179559

166499 (ClinVar)

Gene: USH2A
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 201650f0-4a5b-446d-98e4-65dbae845631
Approved on: 2025-05-21
Published on: 2025-06-30

HGVS expressions

NM_206933.2:c.5039A>G
NM_206933.2(USH2A):c.5039A>G (p.Lys1680Arg)
NC_000001.11:g.216084826T>C
CM000663.2:g.216084826T>C
NC_000001.10:g.216258168T>C
CM000663.1:g.216258168T>C
NC_000001.9:g.214324791T>C
NG_009497.1:g.343571A>G
NG_009497.2:g.343623A>G
ENST00000307340.8:c.5039A>G
ENST00000674083.1:c.5039A>G
ENST00000307340.7:c.5039A>G
ENST00000463147.1:n.283A>G
ENST00000481786.1:n.281A>G
NR_125992.1:n.266-1896T>C
NR_125993.1:n.137-1896T>C
NM_206933.3:c.5039A>G
NM_206933.4:c.5039A>G
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Uncertain Significance

Met criteria codes 2
PP4 PM3_Supporting
Not Met criteria codes 24
BP5 BP7 BP2 BP3 BP1 BP4 PS2 PS4 PS3 PS1 BA1 PP1 PP2 PP3 PM1 PM4 PM5 PM6 PM2 BS4 BS3 BS1 BS2 PVS1

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

PDF
Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The c.5039A>G (p.Lys1680Arg) variant in USH2A is a missense variant that replaces lysine with arginine at codon 1680. (Add gnomad information) The REVEL score for this variant is 0.252, which does not meet the threshold for PP3. This variant has been observed in the homozygous state in one individual with a clinical diagnosis of Usher syndrome (PMID: 36909829), meeting PM3_Supporting. The phenotype observed is highly specific for Usher syndrome, meeting PP4. In summary, this variant meets criteria to be classified as uncertain significance for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: PM3_Supporting, PP4. (ClinGen Hearing Loss VCEP specifications version 2; 5/21/2025)
Met criteria codes
PP4
The variant has been reported in one homozygous proband, who was diagnosed with Usher syndrome.
PM3_Supporting
The variant has been reported in one homozygous proband, who was diagnosed with Usher syndrome.
Not Met criteria codes
BP5
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
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
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
The REVEL computational prediction analysis tool produced a score of 0.252, which also meets no codes.
PS2
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
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
The variant is present in 0.05% Latino alleles in gnomAD.
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
The REVEL computational prediction analysis tool produced a score of 0.252, which also meets no codes.
PM1
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
PM5
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
PM2
The MAF is 0.00057 (20/35312 alleles, 0 homozygotes) for the Latino population, which meets no codes.
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The variant is present in 0.05% Latino alleles in gnomAD.
BS2
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
Curation History
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