1-54139645-TG-TGGGG

Position:

• chr1-54139645-TG-TGGGG

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PM4_Supporting BA1

The NM_201546.5(CDCP2):​c.1222_1224dupCCC​(p.Pro408dup) variant causes a conservative inframe insertion 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. Synonymous variant affecting the same amino acid position (i.e. P408P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.016 (43 hom., cov: 28)
  • Exomes 𝑓: 0.013 (155 hom.)
• Consequence: CDCP2 NM_201546.5 conservative_inframe_insertion
• 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 -7 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_201546.5. Strenght limited to Supporting due to length of the change: 1aa.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.1117+105_1117+107dupCCC		intron_variant		ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.1222_1224dupCCC	p.Pro408dup	conservative_inframe_insertion	4/4		NP_963840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCP2	ENST00000530059.3	c.1117+105_1117+107dupCCC		intron_variant		5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1281+105_*1281+107dupCCC		intron_variant		5		ENSP00000490901.1
CDCP2	ENST00000371330.1	c.1222_1224dupCCC	p.Pro408dup	conservative_inframe_insertion	4/4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2	n.1640_1642dupGGG		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.0160 AC: 1621 AN: 101298 Hom.: 43 Cov.: 28

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

GnomAD3 exomes AF: 0.0333 AC: 5208 AN: 156162 Hom.: 44 AF XY: 0.0382 AC XY: 3253 AN XY: 85076

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 SAS exome AF: 0.122

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.: 59 AF XY: 0.0158 AC XY: 11187 AN XY: 708898

Gnomad4 AFR exome AF: 0.00195

Gnomad4 AMR exome AF: 0.00858

Gnomad4 ASJ exome AF: 0.00295

Gnomad4 EAS exome AF: 0.0334

Gnomad4 SAS exome AF: 0.0972

Gnomad4 FIN exome AF: 0.0423

Gnomad4 NFE exome AF: 0.00537

Gnomad4 OTH exome AF: 0.0153

GnomAD4 genome AF: 0.0160 AC: 1621 AN: 101418 Hom.: 43 Cov.: 28 AF XY: 0.0203 AC XY: 1013 AN XY: 50008

Gnomad4 AFR AF: 0.00183

Gnomad4 AMR AF: 0.00727

Gnomad4 ASJ AF: 0.00142

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0710

Gnomad4 NFE AF: 0.00935

Gnomad4 OTH AF: 0.0137

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;