Genetic Variant CDCP2:c.1117+104_1117+107dupCCCC (chr1-54139645-T-TGGGG) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_201546.5(CDCP2):c.1221_1224dupCCCC(p.Met409ProfsTer46) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000684 in 1,533,118 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0014 ( 2 hom., cov: 28)

Exomes 𝑓: 0.00063 ( 1 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: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 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+104_1117+107dupCCCC		intron	N/A	NP_001340584.1	Q5VXM1-3
	CDCP2	NM_201546.5		c.1221_1224dupCCCC	p.Met409ProfsTer46	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+104_1117+107dupCCCC		intron	N/A	ENSP00000489959.1	Q5VXM1-3
ENSG00000256407	ENST00000637610.1	TSL:5	n.1281+104_1281+107dupCCCC		intron	N/A	ENSP00000490901.1	A0A1B0GWF0
CDCP2	ENST00000371330.1	TSL:2	c.1221_1224dupCCCC	p.Met409ProfsTer46	frameshift	Exon 4 of 4	ENSP00000360381.1	Q5VXM1-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

143

AN:

101544

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000593

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0514

Gnomad EAS

AF:

0.00141

Gnomad SAS

AF:

0.00221

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000429

Gnomad OTH

AF:

0.00146

GnomAD2 exomes

AF:

0.00152

AC:

238

AN:

156162

AF XY:

0.00168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000157

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.000152

Gnomad NFE exome

AF:

0.000319

Gnomad OTH exome

AF:

0.00190

GnomAD4 exome

AF:

0.000633

AC:

906

AN:

1431454

Hom.:

Cov.:

AF XY:

0.000707

AC XY:

504

AN XY:

712422

show subpopulations

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

African (AFR)

AF:

0.0000604

AC:

AN:

33088

American (AMR)

AF:

0.000115

AC:

AN:

43604

Ashkenazi Jewish (ASJ)

AF:

0.0201

AC:

504

AN:

25056

East Asian (EAS)

AF:

0.000846

AC:

AN:

39010

South Asian (SAS)

AF:

0.00186

AC:

157

AN:

84204

European-Finnish (FIN)

AF:

0.0000756

AC:

AN:

52918

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.0000836

AC:

AN:

1088602

Other (OTH)

AF:

0.00186

AC:

110

AN:

59298

⚠️ 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: 0.281

Heterozygous variant carriers

171

256

342

427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.00140

AC:

142

AN:

101664

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

50160

show subpopulations

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

African (AFR)

AF:

0.0000591

AC:

AN:

33844

American (AMR)

AF:

0.00

AC:

AN:

9086

Ashkenazi Jewish (ASJ)

AF:

0.0514

AC:

108

AN:

2100

East Asian (EAS)

AF:

0.00142

AC:

AN:

4234

South Asian (SAS)

AF:

0.00193

AC:

AN:

3626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6864

Middle Eastern (MID)

AF:

0.00

AC:

AN:

190

European-Non Finnish (NFE)

AF:

0.000429

AC:

AN:

39610

Other (OTH)

AF:

0.00143

AC:

AN:

1394

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.329

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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.60

Mutation Taster

=138/62

polymorphism

(source)

Splicing

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

Publications

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1-54139645-TG-TGGGGG

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