Genetic Variant NM_001353655.3:c.1117+105_1117+107dupCCC (chr1-54139645-T-TGGG) – 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+105_1117+107dupCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,525,900 control chromosomes in the GnomAD database, including 198 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.016 ( 43 hom., cov: 28)

Exomes 𝑓: 0.013 ( 155 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCP2	NM_001353655.3 link	c.1117+105_1117+107dupCCC		intron_variant	Intron 4 of 5	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5 link	c.1222_1224dupCCC	p.Pro408dup	conservative_inframe_insertion	Exon 4 of 4		NP_963840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CDCP2	ENST00000530059.3 link	c.1117+105_1117+107dupCCC		intron_variant	Intron 4 of 5	5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1 link	n.1281+105_1281+107dupCCC		intron_variant	Intron 8 of 9	5		ENSP00000490901.1
CDCP2	ENST00000371330.1 link	c.1222_1224dupCCC	p.Pro408dup	conservative_inframe_insertion	Exon 4 of 4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2 link	n.1640_1642dupGGG		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0160

AC:

1621

AN:

101298

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.0112

Gnomad AMR

AF:

0.00728

Gnomad ASJ

AF:

0.00142

Gnomad EAS

AF:

0.0374

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0710

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00935

Gnomad OTH

AF:

0.0139

GnomAD2 exomes

AF:

0.0333

AC:

5208

AN:

156162

AF XY:

0.0382

show subpopulations

Gnomad AFR exome

AF:

0.00194

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.00591

Gnomad EAS exome

AF:

0.0452

Gnomad FIN exome

AF:

0.0625

Gnomad NFE exome

AF:

0.00960

Gnomad OTH exome

AF:

0.0236

GnomAD4 exome

AF:

0.0132

AC:

18845

AN:

1424482

Hom.:

155

Cov.:

AF XY:

0.0158

AC XY:

11187

AN XY:

708898

show subpopulations

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

African (AFR)

AF:

0.00195

AC:

AN:

32852

American (AMR)

AF:

0.00858

AC:

370

AN:

43144

Ashkenazi Jewish (ASJ)

AF:

0.00295

AC:

AN:

25438

East Asian (EAS)

AF:

0.0334

AC:

1260

AN:

37728

South Asian (SAS)

AF:

0.0972

AC:

8118

AN:

83498

European-Finnish (FIN)

AF:

0.0423

AC:

2192

AN:

51870

Middle Eastern (MID)

AF:

0.00620

AC:

AN:

5646

European-Non Finnish (NFE)

AF:

0.00537

AC:

5829

AN:

1085248

Other (OTH)

AF:

0.0153

AC:

902

AN:

59058

⚠️ 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: 0.337

Heterozygous variant carriers

1059

2118

3177

4236

5295

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.0160

AC:

1621

AN:

101418

Hom.:

Cov.:

AF XY:

0.0203

AC XY:

1013

AN XY:

50008

show subpopulations

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

African (AFR)

AF:

0.00183

AC:

AN:

33830

American (AMR)

AF:

0.00727

AC:

AN:

9074

Ashkenazi Jewish (ASJ)

AF:

0.00142

AC:

AN:

2118

East Asian (EAS)

AF:

0.0375

AC:

158

AN:

4216

South Asian (SAS)

AF:

0.128

AC:

455

AN:

3556

European-Finnish (FIN)

AF:

0.0710

AC:

480

AN:

6762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

190

European-Non Finnish (NFE)

AF:

0.00935

AC:

370

AN:

39568

Other (OTH)

AF:

0.0137

AC:

AN:

1390

⚠️ 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: 0.374

Heterozygous variant carriers

133

200

266

333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<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

=84/16

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over