rs2305207
Positions:
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_022124.6(CDH23):c.1270G>A(p.Val424Met) variant causes a missense change. The variant allele was found at a frequency of 0.000107 in 1,612,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000072 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
CDH23
NM_022124.6 missense
NM_022124.6 missense
Scores
6
12
Clinical Significance
Conservation
PhyloP100: 4.53
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.032257378).
BP6
?
Variant 10-71645960-G-A is Benign according to our data. Variant chr10-71645960-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1006937.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr10-71645960-G-A is described in Lovd as [Likely_benign].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDH23 | NM_022124.6 | c.1270G>A | p.Val424Met | missense_variant | 13/70 | ENST00000224721.12 | |
CDH23 | NM_001171930.2 | c.1270G>A | p.Val424Met | missense_variant | 13/32 | ||
CDH23 | NM_001171931.2 | c.1270G>A | p.Val424Met | missense_variant | 13/26 | ||
CDH23 | NM_052836.4 | c.1270G>A | p.Val424Met | missense_variant | 13/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDH23 | ENST00000224721.12 | c.1270G>A | p.Val424Met | missense_variant | 13/70 | 5 | NM_022124.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152232Hom.: 1 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
11
AN:
152232
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000198 AC: 49AN: 247700Hom.: 0 AF XY: 0.000283 AC XY: 38AN XY: 134464
GnomAD3 exomes
AF:
AC:
49
AN:
247700
Hom.:
AF XY:
AC XY:
38
AN XY:
134464
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000110 AC: 161AN: 1460566Hom.: 0 Cov.: 32 AF XY: 0.000151 AC XY: 110AN XY: 726570
GnomAD4 exome
AF:
AC:
161
AN:
1460566
Hom.:
Cov.:
32
AF XY:
AC XY:
110
AN XY:
726570
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152350Hom.: 1 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74496
GnomAD4 genome
?
AF:
AC:
11
AN:
152350
Hom.:
Cov.:
33
AF XY:
AC XY:
7
AN XY:
74496
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
23
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 12;C1832845:Usher syndrome type 1D;C4539685:Pituitary adenoma 5, multiple types Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 24, 2021 | - - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 12, 2020 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;.;.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;.;.;.;.;N;.
REVEL
Benign
Sift
Benign
T;.;.;.;.;.;.;D;.
Sift4G
Uncertain
D;D;.;D;D;D;D;.;.
Polyphen
0.97, 0.99
.;.;D;D;.;.;.;.;.
Vest4
MutPred
Gain of phosphorylation at Y421 (P = 0.18);Gain of phosphorylation at Y421 (P = 0.18);Gain of phosphorylation at Y421 (P = 0.18);Gain of phosphorylation at Y421 (P = 0.18);Gain of phosphorylation at Y421 (P = 0.18);.;Gain of phosphorylation at Y421 (P = 0.18);Gain of phosphorylation at Y421 (P = 0.18);.;
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at