1-54139645-T-TGC

Position:

• chr1-54139645-T-TGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_201546.5(CDCP2):​c.1224_1225insGC​(p.Met409fs) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.597

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]

ENSG00000256407 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.1117+107_1117+108insGC		intron_variant		ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.1224_1225insGC	p.Met409fs	frameshift_variant	4/4		NP_963840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCP2	ENST00000530059.3	c.1117+107_1117+108insGC		intron_variant		5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1281+107_*1281+108insGC		intron_variant		5		ENSP00000490901.1
CDCP2	ENST00000371330.1	c.1224_1225insGC	p.Met409fs	frameshift_variant	4/4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2	n.1635_1636insCG		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.00521 AC: 529 AN: 101576 Hom.: 1 Cov.: 28

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.: 6 AF XY: 0.00563 AC XY: 479 AN XY: 85076

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.: 19 Cov.: 59 AF XY: 0.00374 AC XY: 2671 AN XY: 713226

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.: 1 Cov.: 28 AF XY: 0.00456 AC XY: 229 AN XY: 50176

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

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

CDCP2: BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553173737; hg19: chr1-54605318;