Genetic Variant CDCP2:c.1117+106_1117+107dupCC (chr1-54139645-T-TGG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_201546.5(CDCP2):c.1223_1224dupCC(p.Met409ProfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,530,242 control chromosomes in the GnomAD database, including 10,485 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 1795 hom., cov: 28)

Exomes 𝑓: 0.12 ( 8690 hom. )

Consequence

CDCP2
NM_201546.5 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.597

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

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+106_1117+107dupCC		intron	N/A	NP_001340584.1	Q5VXM1-3
	CDCP2	NM_201546.5		c.1223_1224dupCC	p.Met409ProfsTer2	frameshift	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+106_1117+107dupCC		intron	N/A	ENSP00000489959.1	Q5VXM1-3
ENSG00000256407	ENST00000637610.1	TSL:5	n.1281+106_1281+107dupCC		intron	N/A	ENSP00000490901.1	A0A1B0GWF0
CDCP2	ENST00000371330.1	TSL:2	c.1223_1224dupCC	p.Met409ProfsTer2	frameshift	Exon 4 of 4	ENSP00000360381.1	Q5VXM1-1

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

21994

AN:

101144

Hom.:

1791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.203

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.284

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.184

Gnomad OTH

AF:

0.209

GnomAD2 exomes

AF:

0.229

AC:

35706

AN:

156162

AF XY:

0.221

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.414

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.174

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.124

AC:

176974

AN:

1428978

Hom.:

8690

Cov.:

AF XY:

0.124

AC XY:

87927

AN XY:

711232

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.166

AC:

5465

AN:

32972

American (AMR)

AF:

0.198

AC:

8589

AN:

43466

Ashkenazi Jewish (ASJ)

AF:

0.103

AC:

2636

AN:

25482

East Asian (EAS)

AF:

0.337

AC:

13141

AN:

38970

South Asian (SAS)

AF:

0.151

AC:

12688

AN:

84236

European-Finnish (FIN)

AF:

0.165

AC:

8673

AN:

52650

Middle Eastern (MID)

AF:

0.125

AC:

707

AN:

5650

European-Non Finnish (NFE)

AF:

0.108

AC:

117475

AN:

1086238

Other (OTH)

AF:

0.128

AC:

7600

AN:

59314

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.398

Heterozygous variant carriers

8424

16848

25273

33697

42121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4640

9280

13920

18560

23200

<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:

0.217

AC:

22008

AN:

101264

Hom.:

1795

Cov.:

AF XY:

0.225

AC XY:

11224

AN XY:

49936

show subpopulations

African (AFR)

AF:

0.203

AC:

6834

AN:

33688

American (AMR)

AF:

0.284

AC:

2570

AN:

9052

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

394

AN:

2116

East Asian (EAS)

AF:

0.446

AC:

1873

AN:

4202

South Asian (SAS)

AF:

0.208

AC:

749

AN:

3606

European-Finnish (FIN)

AF:

0.272

AC:

1851

AN:

6798

Middle Eastern (MID)

AF:

0.258

AC:

AN:

190

European-Non Finnish (NFE)

AF:

0.184

AC:

7283

AN:

39512

Other (OTH)

AF:

0.216

AC:

299

AN:

1386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.437

Heterozygous variant carriers

827

1654

2481

3308

4135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.60

Mutation Taster

=197/3

polymorphism (auto)

(source)

Splicing

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

Publications

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1-54139645-TG-TGGG

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