5-176568773-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017675.6(CDHR2):​c.220C>T​(p.Pro74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CDHR2
NM_017675.6 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -9.44
Variant links:
Genes affected
CDHR2 (HGNC:18231): (cadherin related family member 2) This gene is a member of the protocadherin family, which represents a subset of the larger cadherin superfamily. The members of the protocadherin family encode non-classical cadherins that function as calcium-dependent cell-cell adhesion molecules. This protocadherin represents a new candidate for tumor suppression. Alternatively spliced transcript variants that encode the same protein have been identified. [provided by RefSeq, Jan 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.036524028).
BP6
Variant 5-176568773-C-T is Benign according to our data. Variant chr5-176568773-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3830237.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDHR2NM_017675.6 linkc.220C>T p.Pro74Ser missense_variant Exon 4 of 32 ENST00000261944.10 NP_060145.3 Q9BYE9
CDHR2NM_001171976.2 linkc.220C>T p.Pro74Ser missense_variant Exon 4 of 32 NP_001165447.1 Q9BYE9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDHR2ENST00000261944.10 linkc.220C>T p.Pro74Ser missense_variant Exon 4 of 32 1 NM_017675.6 ENSP00000261944.5 Q9BYE9
CDHR2ENST00000510636.5 linkc.220C>T p.Pro74Ser missense_variant Exon 4 of 32 1 ENSP00000424565.1 Q9BYE9
CDHR2ENST00000506348.1 linkn.267C>T non_coding_transcript_exon_variant Exon 3 of 31 1
CDHR2ENST00000510124.5 linkn.*200C>T downstream_gene_variant 5 ENSP00000426838.1 D6REJ3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152238
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251422
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135902
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1461870
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152238
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 07, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.0010
DANN
Benign
0.13
DEOGEN2
Benign
0.00017
T;T;T
Eigen
Benign
-2.5
Eigen_PC
Benign
-2.6
FATHMM_MKL
Benign
0.0021
N
LIST_S2
Benign
0.31
.;.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.037
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.56
N;N;N
PrimateAI
Benign
0.21
T
PROVEAN
Benign
0.32
N;N;N
REVEL
Benign
0.031
Sift
Benign
0.71
T;T;T
Sift4G
Benign
0.69
T;T;T
Polyphen
0.0010
B;B;B
Vest4
0.058
MutPred
0.36
Gain of disorder (P = 0.0819);Gain of disorder (P = 0.0819);Gain of disorder (P = 0.0819);
MVP
0.085
MPC
0.15
ClinPred
0.029
T
GERP RS
-9.6
Varity_R
0.053
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs746271410; hg19: chr5-175995774; API