chr1-54139645-T-TG

Position:

• chr1-54139645-T-TG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_201546.5(CDCP2):​c.1224dupC​(p.Met409fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,534,020 control chromosomes in the GnomAD database, including 25,277 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P408P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.27 (2569 hom., cov: 28)
  • Exomes 𝑓: 0.18 (22708 hom.)
• Consequence: CDCP2 NM_201546.5 frameshift
• Clinical Significance: Not reported in ClinVar
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.1117+107dupC		intron_variant		ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.1224dupC	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+107dupC		intron_variant		5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1281+107dupC		intron_variant		5		ENSP00000490901.1
CDCP2	ENST00000371330.1	c.1224dupC	p.Met409fs	frameshift_variant	4/4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2	n.1642dupG		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.268 AC: 27251 AN: 101506 Hom.: 2564 Cov.: 28

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.263 AC: 41098 AN: 156162 Hom.: 3272 AF XY: 0.270 AC XY: 22965 AN XY: 85076

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.316

Gnomad EAS exome AF: 0.200

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.313

Gnomad OTH exome AF: 0.267

GnomAD4 exome AF: 0.182 AC: 261014 AN: 1432394 Hom.: 22708 Cov.: 59 AF XY: 0.184 AC XY: 131048 AN XY: 713048

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.0958

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.185

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.268 AC: 27282 AN: 101626 Hom.: 2569 Cov.: 28 AF XY: 0.264 AC XY: 13233 AN XY: 50142

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3841798; hg19: chr1-54605318;