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]

Variant: NM_022124.5(CDH23):c.9566G>A (p.Arg3189Gln)

CA175533

162956 (ClinVar)

Gene: CDH23
Condition: Usher syndrome
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: f7c337df-9d3f-48fe-afac-1a5ce74511bd
Approved on: 2023-01-18
Published on: 2023-02-06

HGVS expressions

NM_022124.5:c.9566G>A
NM_022124.5(CDH23):c.9566G>A (p.Arg3189Gln)
NC_000010.11:g.71812823G>A
CM000672.2:g.71812823G>A
NC_000010.10:g.73572580G>A
CM000672.1:g.73572580G>A
NC_000010.9:g.73242586G>A
NG_008835.1:g.420877G>A
ENST00000224721.12:c.9566G>A
ENST00000642965.1:n.3499G>A
ENST00000647092.1:n.3163G>A
ENST00000224721.10:c.9581G>A
ENST00000398788.4:c.2846G>A
ENST00000475158.1:n.3102G>A
ENST00000619887.4:c.2846G>A
ENST00000622827.4:c.9566G>A
NM_001171933.1:c.2846G>A
NM_001171934.1:c.2846G>A
NM_001171935.1:c.257G>A
NM_001171936.1:c.257G>A
NM_022124.6:c.9566G>A
NM_022124.6(CDH23):c.9566G>A (p.Arg3189Gln)
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Uncertain Significance

The Expert Panel has overridden the computationally generated classification - "[unknown]"
Not Met criteria codes 26
BS2 BS3 BS4 BS1 BP5 BP7 BP3 BP2 BP4 BP1 PS1 PS3 PS4 PS2 PP1 PP4 PP3 PP2 BA1 PVS1 PM6 PM2 PM5 PM4 PM3 PM1

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hearing Loss VCEP
The NM_022124.6:c.9566G>A variant in the CDH23 gene is a missense variant predicted to cause substitution of arginine by glutamine at amino acid 3189 (p.Arg3189Gln). This variant has been identified in 1 heterozygous patient with sensorineural hearing loss (Partners LMM internal data, SCV000197429.4). The highest population minor allele frequency of the variant is 0.023% (7/30430) of South Asian alleles in gnomAD v.2.1.1, which does not meet any of the criteria for PM2_P, BA1, and BS1. The REVEL computational prediction analysis tool produced a score of 0.683 which does not meet the criteria for PP3. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive Usher syndrome. ACMG/AMP criteria applied as specified by the ClinGen Hearing Loss VCEP: None (ClinGen Hearing Loss VCEP specifications version 2; 1/18/2022).
Not Met criteria codes
BS2
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
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
The highest population minor allele frequency is 0.023% (7/30430) of South Asian alleles in gnomAD v.2.1.1, which does not meet PM2_P, BA1, and BS1
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
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
BP4
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
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
LMM: Variant was identified in one heterozygous individual with sensorineural hearing loss. No other variant detected.
PS2
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
PP3
REVEL score 0.683
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
The highest population minor allele frequency is 0.023% (7/30430) of South Asian alleles in gnomAD v.2.1.1, which does not meet PM2_P, BA1, and BS1
PVS1
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 highest population minor allele frequency is 0.023% (7/30430) of South Asian alleles in gnomAD v.2.1.1, which does not meet PM2_P, BA1, and BS1
PM5
NM_022124.5(CDH23):c.9565C>T (p.Arg3189Trp). ClinVar ID: 4926. Variant is VUS.
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
1 heterozygous patient with sensorineural hearing loss was identified with the variant but was not scored (Partners LMM internal data, SCV000197429.4)
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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