Variant 1-54139569-G-A 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_201546.5(CDCP2):c.1301C>T(p.Thr434Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000791 in 1,613,064 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00050 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 1 hom. )

Consequence

CDCP2
NM_201546.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.57

Variant links:

Genes affected

CDCP2 (HGNC:27297): (CUB domain containing protein 2) Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CDCP2 links:

ENSG00000256407 (HGNC:):

ENSG00000256407 links:

Genome browser will be placed here

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=0.009737581).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3 linkuse as main transcript	c.1117+184C>T		intron_variant		ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5 linkuse as main transcript	c.1301C>T	p.Thr434Met	missense_variant	4/4		NP_963840.2	Q5VXM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDCP2	ENST00000530059.3 linkuse as main transcript	c.1117+184C>T		intron_variant		5	NM_001353655.3	ENSP00000489959.1	A0A1B0GU47
ENSG00000256407	ENST00000637610.1 linkuse as main transcript	n.*1281+184C>T		intron_variant		5		ENSP00000490901.1	A0A1B0GWF0
CDCP2	ENST00000371330.1 linkuse as main transcript	c.1301C>T	p.Thr434Met	missense_variant	4/4	2		ENSP00000360381.1	Q5VXM1-1
ENSG00000280425	ENST00000623663.2 linkuse as main transcript	n.1558G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.000500

AC:

AN:

151870

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00106

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000490

AC:

123

AN:

250780

Hom.:

AF XY:

0.000472

AC XY:

AN XY:

135546

show subpopulations

Gnomad AFR exome

AF:

0.0000617

Gnomad AMR exome

AF:

0.000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000926

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.000821

AC:

1200

AN:

1461076

Hom.:

Cov.:

AF XY:

0.000732

AC XY:

532

AN XY:

726844

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000336

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.000973

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.000500

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.000471

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000787

Hom.:

Bravo

AF:

0.000548

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000527

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000889

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

May 06, 2024

The c.1301C>T (p.T434M) alteration is located in exon 4 (coding exon 4) of the CDCP2 gene. This alteration results from a C to T substitution at nucleotide position 1301, causing the threonine (T) at amino acid position 434 to be replaced by a methionine (M). 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

0.12

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.12

DANN

Benign

0.95

DEOGEN2

Benign

0.013

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00097

LIST_S2

Benign

0.39

M_CAP

Benign

0.0018

MetaRNN

Benign

0.0097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.2

REVEL

Benign

0.015

Sift

Pathogenic

0.0

Sift4G

Benign

0.070

Polyphen

0.0020

Vest4

0.067

MVP

0.067

MPC

0.051

ClinPred

0.017

GERP RS

-4.8

Varity_R

0.029

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