dbSNP rs146464941: CDCP2:c.1117+175T>C (chr1-54139578-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_201546.5(CDCP2):c.1292T>C(p.Leu431Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000836 in 1,613,166 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.00086 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 3 hom. )

Consequence

CDCP2
NM_201546.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.04

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004274398).

BP6

Variant 1-54139578-A-G is Benign according to our data. Variant chr1-54139578-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2351538.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201546.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCP2	NM_001353655.3	MANE Select	c.1117+175T>C		intron	N/A	NP_001340584.1	Q5VXM1-3
	CDCP2	NM_201546.5		c.1292T>C	p.Leu431Pro	missense	Exon 4 of 4	NP_963840.2	Q5VXM1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CDCP2	ENST00000530059.3	TSL:5 MANE Select	c.1117+175T>C		intron	N/A	ENSP00000489959.1	Q5VXM1-3
ENSG00000256407	ENST00000637610.1	TSL:5	n.*1281+175T>C		intron	N/A	ENSP00000490901.1	A0A1B0GWF0
CDCP2	ENST00000371330.1	TSL:2	c.1292T>C	p.Leu431Pro	missense	Exon 4 of 4	ENSP00000360381.1	Q5VXM1-1

Frequencies

GnomAD3 genomes

AF:

0.000856

AC:

130

AN:

151788

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00289

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000213

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000941

AC:

236

AN:

250910

AF XY:

0.000936

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000812

Gnomad ASJ exome

AF:

0.00388

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00130

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000834

AC:

1218

AN:

1461262

Hom.:

Cov.:

AF XY:

0.000860

AC XY:

625

AN XY:

726928

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.00123

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00283

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39574

South Asian (SAS)

AF:

0.000337

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53240

Middle Eastern (MID)

AF:

0.00468

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000845

AC:

940

AN:

1111854

Other (OTH)

AF:

0.00147

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

140

209

279

349

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000856

AC:

130

AN:

151904

Hom.:

Cov.:

AF XY:

0.000754

AC XY:

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41536

American (AMR)

AF:

0.00209

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00289

AC:

AN:

3466

East Asian (EAS)

AF:

0.000196

AC:

AN:

5112

South Asian (SAS)

AF:

0.000213

AC:

AN:

4690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00106

AC:

AN:

68006

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000982

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000898

AC:

109

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00196

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.45

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0095

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.27

M_CAP

Benign

0.0032

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.93

REVEL

Benign

0.096

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.066

Vest4

0.053

MVP

0.076

MPC

0.074

ClinPred

0.013

GERP RS

-6.5

Varity_R

0.34

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over