Variant: NM_022124.5(CDH23):c.380A>G (p.Asp127Gly)

CA10576804

228491 (ClinVar)

Gene: CDH23

Condition: Usher syndrome

Inheritance Mode: Autosomal recessive inheritance

UUID: 637bd8ea-a91f-4012-9a60-43d0bfce68ad

Approved on: 2018-09-10

Published on: 2019-07-17

HGVS expressions

NM_022124.5:c.380A>G
NM_022124.5(CDH23):c.380A>G (p.Asp127Gly)
NC_000010.11:g.71511163A>G
CM000672.2:g.71511163A>G
NC_000010.10:g.73270920A>G
CM000672.1:g.73270920A>G
NC_000010.9:g.72940926A>G
NG_008835.1:g.119217A>G
ENST00000224721.12:c.380A>G
ENST00000398809.9:c.380A>G
ENST00000442677.4:c.380A>G
ENST00000646131.1:c.44A>G
ENST00000224721.10:c.380A>G
ENST00000299366.11:c.380A>G
ENST00000398809.8:c.380A>G
ENST00000398842.7:c.203A>G
ENST00000461841.7:c.380A>G
ENST00000616684.4:c.380A>G
ENST00000622827.4:c.380A>G
NM_001171930.1:c.380A>G
NM_001171931.1:c.380A>G
NM_001171932.1:c.380A>G
NM_052836.3:c.380A>G
NR_120672.1:n.143+615T>C
NM_001171930.2:c.380A>G
NM_001171931.2:c.380A>G
NM_022124.6:c.380A>G
NM_052836.4:c.380A>G
NM_001171932.2:c.380A>G

Likely Pathogenic

• Met criteria codes: PM2 PM3 PP3 PP4

• Not Met criteria codes: BS2 BS1 BS4 BS3 BP4 BP3 BP1 BP2 BP5 BP7 PM6 PM1 PM5 PM4 PS1 PS2 PS3 PS4 BA1 PP1 PP2 PVS1

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Evidence submitted by expert panel

Hearing Loss VCEP

The p.Asp127Gly variant in CDH23 was absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org) (PM2). Computational prediction analysis using the metapredictor tool REVEL suggests that the variant may impact the protein (PP3). This variant has been detected in 1 patient with hearing loss in trans with a pathogenic variant (PM3; Partners LMM internal data SCV000271558.2). The patient with this variant displayed features of congenital severe-profound hearing loss with vestibular dysfunction and ophthalmic findings which are consistent with Usher syndrome (PP4). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recession Usher syndrome based on the ACMG/AMP criteria applied (PM2, PM3, PP3, PP4).

Met criteria codes

• PM2: Absent from gnomAD
• PM3: In trans with NM_022124.5:c.1949_1950insC (p.Leu651fs) in CDH23 (Laboratory for Molecular Medicine Internal Data).
• PP3: REVEL score is 0.796
• PP4: Patient with congenital severe-profound hearing loss with vestibular dysfunction and ophthalmic findings indicative of Usher syndrome (Laboratory for Molecular Medicine Internal Data).

Not Met criteria codes

• BS2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: Absent from gnomAD
• 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
• BP4: REVEL score is 0.796
• 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
• BP2: 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
• BP7: 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
• 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
• PS1: 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
• 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
• BA1: Absent from 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
• PVS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline