Variant 5-176568722-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017675.6(CDHR2):c.169C>T(p.Pro57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,244 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)

Consequence

CDHR2
NM_017675.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.91

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]

CDHR2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029888004).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDHR2	NM_017675.6 linkuse as main transcript	c.169C>T	p.Pro57Ser	missense_variant	4/32	ENST00000261944.10	NP_060145.3
CDHR2	NM_001171976.2 linkuse as main transcript	c.169C>T	p.Pro57Ser	missense_variant	4/32		NP_001165447.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CDHR2	ENST00000261944.10 linkuse as main transcript	c.169C>T	p.Pro57Ser	missense_variant	4/32	1	NM_017675.6	ENSP00000261944	P1
CDHR2	ENST00000510636.5 linkuse as main transcript	c.169C>T	p.Pro57Ser	missense_variant	4/32	1		ENSP00000424565	P1
CDHR2	ENST00000506348.1 linkuse as main transcript	n.216C>T		non_coding_transcript_exon_variant	3/31	1
CDHR2	ENST00000510124.5 linkuse as main transcript	c.*149C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	5		ENSP00000426838

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.169C>T (p.P57S) alteration is located in exon 4 (coding exon 3) of the CDHR2 gene. This alteration results from a C to T substitution at nucleotide position 169, causing the proline (P) at amino acid position 57 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0020

DANN

Benign

0.42

DEOGEN2

Benign

0.020

T;T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.38

.;.;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.030

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.040

Sift

Benign

0.38

T;T;T

Sift4G

Benign

0.67

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.14

MutPred

0.26

Gain of disorder (P = 0.1019);Gain of disorder (P = 0.1019);Gain of disorder (P = 0.1019);

MVP

0.092

MPC

0.15

ClinPred

0.033

GERP RS

-7.2

Varity_R

0.068

gMVP

0.35

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over