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_001353655.3(CDCP2):c.1117+104_1117+107dupCCCC variant causes a intron 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_001353655.3 intron

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCP2	NM_001353655.3 link	c.1117+104_1117+107dupCCCC		intron_variant	Intron 4 of 5	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5 link	c.1221_1224dupCCCC	p.Met409ProfsTer46	frameshift_variant	Exon 4 of 4		NP_963840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CDCP2	ENST00000530059.3 link	c.1117+104_1117+107dupCCCC		intron_variant	Intron 4 of 5	5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1 link	n.1281+104_1281+107dupCCCC		intron_variant	Intron 8 of 9	5		ENSP00000490901.1
CDCP2	ENST00000371330.1 link	c.1221_1224dupCCCC	p.Met409ProfsTer46	frameshift_variant	Exon 4 of 4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2 link	n.1639_1642dupGGGG		non_coding_transcript_exon_variant	Exon 2 of 2	5

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over