Variant 1-54139647-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.1223C>T(p.Pro408Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000695 in 1,222,998 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P408S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

CDCP2
NM_201546.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0870

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=0.007796973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3 link	c.1117+106C>T		intron_variant		ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5 link	c.1223C>T	p.Pro408Leu	missense_variant	4/4		NP_963840.2	Q5VXM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CDCP2	ENST00000530059.3 link	c.1117+106C>T		intron_variant		5	NM_001353655.3	ENSP00000489959.1	A0A1B0GU47
ENSG00000256407	ENST00000637610.1 link	n.*1281+106C>T		intron_variant		5		ENSP00000490901.1	A0A1B0GWF0
CDCP2	ENST00000371330.1 link	c.1223C>T	p.Pro408Leu	missense_variant	4/4	2		ENSP00000360381.1	Q5VXM1-1
ENSG00000280425	ENST00000623663.2 link	n.1636G>A		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes

AF:

0.000267

AC:

AN:

29962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000774

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00140

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000566

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000346

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000359

AC:

AN:

47412

Hom.:

AF XY:

0.000269

AC XY:

AN XY:

26036

show subpopulations

Gnomad AFR exome

AF:

0.000197

Gnomad AMR exome

AF:

0.00206

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000315

Gnomad OTH exome

AF:

0.000998

GnomAD4 exome

AF:

0.0000645

AC:

AN:

1193036

Hom.:

Cov.:

AF XY:

0.0000618

AC XY:

AN XY:

598396

show subpopulations

Gnomad4 AFR exome

AF:

0.0000326

Gnomad4 AMR exome

AF:

0.000244

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000259

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000725

Gnomad4 OTH exome

AF:

0.0000194

GnomAD4 genome

AF:

0.000267

AC:

AN:

29962

Hom.:

Cov.:

AF XY:

0.000266

AC XY:

AN XY:

15056

show subpopulations

Gnomad4 AFR

AF:

0.0000774

Gnomad4 AMR

AF:

0.00140

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000566

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000346

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000185

AC:

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

Sep 17, 2021

The c.1223C>T (p.P408L) 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 1223, causing the proline (P) at amino acid position 408 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.7

DANN

Benign

0.88

DEOGEN2

Benign

0.0041

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.36

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.26

PROVEAN

Benign

0.16

REVEL

Benign

0.0070

Sift

Benign

1.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.13

MutPred

0.27

Loss of loop (P = 0.0073);

MVP

0.17

MPC

0.051

ClinPred

0.018

GERP RS

-0.42

Varity_R

0.020

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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