Genetic Variant CDCP2:c.1117+107_1117+108insGC (chr1-54139645-T-TGC) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_201546.5(CDCP2):c.1224_1225insGC(p.Met409AlafsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,534,478 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P408P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0052 ( 1 hom., cov: 28)

Exomes 𝑓: 0.0037 ( 19 hom. )

Consequence

CDCP2
NM_201546.5 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.597

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 1-54139645-T-TGC is Benign according to our data. Variant chr1-54139645-T-TGC is described in ClinVar as [Likely_benign]. Clinvar id is 2638827.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCP2	NM_001353655.3 link	c.1117+107_1117+108insGC		intron_variant	Intron 4 of 5	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5 link	c.1224_1225insGC	p.Met409AlafsTer2	frameshift_variant	Exon 4 of 4		NP_963840.2	Q5VXM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDCP2	ENST00000530059.3 link	c.1117+107_1117+108insGC		intron_variant	Intron 4 of 5	5	NM_001353655.3	ENSP00000489959.1	A0A1B0GU47
ENSG00000256407	ENST00000637610.1 link	n.1281+107_1281+108insGC		intron_variant	Intron 8 of 9	5		ENSP00000490901.1	A0A1B0GWF0
CDCP2	ENST00000371330.1 link	c.1224_1225insGC	p.Met409AlafsTer2	frameshift_variant	Exon 4 of 4	2		ENSP00000360381.1	Q5VXM1-1
ENSG00000280425	ENST00000623663.2 link	n.1635_1636insCG		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.00521

AC:

529

AN:

101576

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.00661

Gnomad ASJ

AF:

0.0113

Gnomad EAS

AF:

0.000235

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.000437

Gnomad MID

AF:

0.0146

Gnomad NFE

AF:

0.00833

Gnomad OTH

AF:

0.00438

GnomAD3 exomes

AF:

0.00524

AC:

818

AN:

156162

Hom.:

AF XY:

0.00563

AC XY:

479

AN XY:

85076

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.00543

Gnomad ASJ exome

AF:

0.00991

Gnomad EAS exome

AF:

0.0000727

Gnomad SAS exome

AF:

0.00187

Gnomad FIN exome

AF:

0.0000762

Gnomad NFE exome

AF:

0.00862

Gnomad OTH exome

AF:

0.00815

GnomAD4 exome

AF:

0.00374

AC:

5357

AN:

1432782

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

2671

AN XY:

713226

show subpopulations

Gnomad4 AFR exome

AF:

0.00133

Gnomad4 AMR exome

AF:

0.00300

Gnomad4 ASJ exome

AF:

0.00595

Gnomad4 EAS exome

AF:

0.0000256

Gnomad4 SAS exome

AF:

0.00142

Gnomad4 FIN exome

AF:

0.000227

Gnomad4 NFE exome

AF:

0.00421

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00519

AC:

528

AN:

101696

Hom.:

Cov.:

AF XY:

0.00456

AC XY:

229

AN XY:

50176

show subpopulations

Gnomad4 AFR

AF:

0.00157

Gnomad4 AMR

AF:

0.00660

Gnomad4 ASJ

AF:

0.0113

Gnomad4 EAS

AF:

0.000236

Gnomad4 SAS

AF:

0.00248

Gnomad4 FIN

AF:

0.000437

Gnomad4 NFE

AF:

0.00833

Gnomad4 OTH

AF:

0.00431

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CDCP2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over