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]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
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  • See Evidence submitted by expert panel for details.

Variant: NM_004004.5:c.677T>A

CA387460663

585322 (ClinVar)

Gene: GJB2
Condition: nonsyndromic genetic deafness
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 3727aeaa-7c6e-4712-b0f1-b1eea47c7b7f

HGVS expressions

NM_004004.5:c.677T>A
NC_000013.11:g.20188905A>T
CM000675.2:g.20188905A>T
NC_000013.10:g.20763044A>T
CM000675.1:g.20763044A>T
NC_000013.9:g.19661044A>T
NG_008358.1:g.9071T>A
ENST00000382844.2:c.677T>A
ENST00000382848.5:c.677T>A
ENST00000382844.1:c.677T>A
ENST00000382848.4:c.677T>A
NM_004004.6:c.677T>A
NM_004004.6(GJB2):c.677T>A (p.Val226Asp)

Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 25
PP2 PP3 PP4 PP1 PM1 PM3 PM4 PM5 PM6 PVS1 BA1 BS4 BS3 BS1 BS2 BP7 BP5 BP2 BP1 BP4 BP3 PS2 PS4 PS3 PS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The NM_004004.6:c.677T>A variant in GJB2 is a missense variant predicted to cause substitution of valine by aspartic acid at amino acid 226 (p.Val226Asp). The variant was absent from gnomAD v2.1.1 meeting PM2_Supporting. The REVEL computational prediction analysis tool produced a score of 0.57 (PP3/BP4 not met). This variant has been identified in a heterozygous state in one individual with sensorineural hearing loss (PMID: 20201936). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive nonsyndromic hearing loss. ACMG/AMP criteria applied as specified by the ClinGen Hearing Loss VCEP: PM2_Supporting (ClinGen Hearing Loss VCEP specifications version 2; 8/22/2023).
Met criteria codes
PM2_Supporting
The variant was absent from gnomAD v2.1.1 meeting PM2_Supporting.
Not Met criteria codes
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 0.57 (PP3/BP4 not met).
PP4
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
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
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
PVS1
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
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
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
(kiyo) I agree.
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
BP2
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 0.57 (PP3/BP4 not met).
BP3
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
PS4
This variant has been identified in a heterozygous state in one individual with sensorineural hearing loss (PMID: 20201936).
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
Approved on: 2023-08-22
Published on: 2024-01-10
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