chr10-71797096-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000475158.1(CDH23):​n.241G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,260 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CDH23
ENST00000475158.1 non_coding_transcript_exon

Scores

2
Splicing: ADA: 0.00002762
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.426

Publications

1 publications found
Variant links:
Genes affected
CDH23 (HGNC:13733): (cadherin related 23) This gene is a member of the cadherin superfamily, whose genes encode calcium dependent cell-cell adhesion glycoproteins. The encoded protein is thought to be involved in stereocilia organization and hair bundle formation. The gene is located in a region containing the human deafness loci DFNB12 and USH1D. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of this cadherin-like gene. Upregulation of this gene may also be associated with breast cancer. Alternative splice variants encoding different isoforms have been described. [provided by RefSeq, May 2013]
CDH23 Gene-Disease associations (from GenCC):
  • autosomal recessive nonsyndromic hearing loss 12
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
  • nonsyndromic genetic hearing loss
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • Usher syndrome type 1
    Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • Usher syndrome type 1D
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDH23NM_022124.6 linkc.6713-8G>C splice_region_variant, intron_variant Intron 48 of 69 ENST00000224721.12 NP_071407.4 Q9H251-1Q6P152
CDH23NM_001171933.1 linkc.-8-8G>C splice_region_variant, intron_variant Intron 1 of 22 NP_001165404.1 Q9H251-7
CDH23NM_001171934.1 linkc.-8-8G>C splice_region_variant, intron_variant Intron 1 of 21 NP_001165405.1 Q9H251-9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDH23ENST00000224721.12 linkc.6713-8G>C splice_region_variant, intron_variant Intron 48 of 69 5 NM_022124.6 ENSP00000224721.9 Q9H251-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000408
AC:
1
AN:
245384
AF XY:
0.00000751
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1446260
Hom.:
0
Cov.:
27
AF XY:
0.00000139
AC XY:
1
AN XY:
720016
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33170
American (AMR)
AF:
0.00
AC:
0
AN:
44436
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25986
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39564
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85236
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53212
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5608
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1099204
Other (OTH)
AF:
0.00
AC:
0
AN:
59844
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
3.7
DANN
Benign
0.63
PhyloP100
-0.43

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000028
dbscSNV1_RF
Benign
0.0
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs369946986; hg19: chr10-73556853; API