chr1-54139645-T-TGG

Position:

• chr1-54139645-T-TGG

Variant summary

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

The NM_201546.5(CDCP2):​c.1223_1224dupCC​(p.Met409fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,530,242 control chromosomes in the GnomAD database, including 10,485 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 0.22 (1795 hom., cov: 28)
  • Exomes 𝑓: 0.12 (8690 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 (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.1117+106_1117+107dupCC		intron_variant		ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.1223_1224dupCC	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+106_1117+107dupCC		intron_variant		5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1281+106_*1281+107dupCC		intron_variant		5		ENSP00000490901.1
CDCP2	ENST00000371330.1	c.1223_1224dupCC	p.Met409fs	frameshift_variant	4/4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2	n.1641_1642dupGG		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.217 AC: 21994 AN: 101144 Hom.: 1791 Cov.: 28

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.209

GnomAD3 exomes AF: 0.229 AC: 35706 AN: 156162 Hom.: 2055 AF XY: 0.221 AC XY: 18764 AN XY: 85076

Gnomad AFR exome AF: 0.187

Gnomad AMR exome AF: 0.343

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.414

Gnomad SAS exome AF: 0.195

Gnomad FIN exome AF: 0.267

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.124 AC: 176974 AN: 1428978 Hom.: 8690 Cov.: 59 AF XY: 0.124 AC XY: 87927 AN XY: 711232

Gnomad4 AFR exome AF: 0.166

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.165

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.128

GnomAD4 genome AF: 0.217 AC: 22008 AN: 101264 Hom.: 1795 Cov.: 28 AF XY: 0.225 AC XY: 11224 AN XY: 49936

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.216

ClinVar

Not reported in ClinVar

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: rs3841798; hg19: chr1-54605318;