chr1-54139645-T-TGGG

Variant names:

• chr1-54139645-T-TGGG
• rs3841798
• NM_001353655.3:c.1117+105_1117+107dupCCC

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001353655.3(CDCP2):​c.1117+105_1117+107dupCCC variant causes a intron 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.

• Frequency:
  • Genomes: 𝑓 0.016 (43 hom., cov: 28)
  • Exomes 𝑓: 0.013 (155 hom.)
• Consequence: CDCP2 NM_001353655.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 10 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 43 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353655.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCP2	NM_001353655.3	MANE Select	c.1117+105_1117+107dupCCC		intron	N/A	NP_001340584.1
	CDCP2	NM_201546.5		c.1222_1224dupCCC	p.Pro408dup	conservative_inframe_insertion	Exon 4 of 4	NP_963840.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCP2	ENST00000530059.3	TSL:5 MANE Select	c.1117+105_1117+107dupCCC		intron	N/A	ENSP00000489959.1
	ENSG00000256407	ENST00000637610.1	TSL:5	n.*1281+105_*1281+107dupCCC		intron	N/A	ENSP00000490901.1
	CDCP2	ENST00000371330.1	TSL:2	c.1222_1224dupCCC	p.Pro408dup	conservative_inframe_insertion	Exon 4 of 4	ENSP00000360381.1

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

GnomAD2 exomes AF: 0.0333 AC: 5208 AN: 156162 AF XY: 0.0382

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00195 AC: 64 AN: 32852

American (AMR) AF: 0.00858 AC: 370 AN: 43144

Ashkenazi Jewish (ASJ) AF: 0.00295 AC: 75 AN: 25438

East Asian (EAS) AF: 0.0334 AC: 1260 AN: 37728

South Asian (SAS) AF: 0.0972 AC: 8118 AN: 83498

European-Finnish (FIN) AF: 0.0423 AC: 2192 AN: 51870

Middle Eastern (MID) AF: 0.00620 AC: 35 AN: 5646

European-Non Finnish (NFE) AF: 0.00537 AC: 5829 AN: 1085248

Other (OTH) AF: 0.0153 AC: 902 AN: 59058

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00183 AC: 62 AN: 33830

American (AMR) AF: 0.00727 AC: 66 AN: 9074

Ashkenazi Jewish (ASJ) AF: 0.00142 AC: 3 AN: 2118

East Asian (EAS) AF: 0.0375 AC: 158 AN: 4216

South Asian (SAS) AF: 0.128 AC: 455 AN: 3556

European-Finnish (FIN) AF: 0.0710 AC: 480 AN: 6762

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 190

European-Non Finnish (NFE) AF: 0.00935 AC: 370 AN: 39568

Other (OTH) AF: 0.0137 AC: 19 AN: 1390

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60
Mutation Taster		=84/16	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3841798; hg19: chr1-54605318; COSMIC: COSV106060926; COSMIC: COSV106060926;