chr1-54139645-T-TGGGG

Position:

• chr1-54139645-T-TGGGG

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_201546.5(CDCP2):​c.1221_1224dupCCCC​(p.Met409fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000684 in 1,533,118 control chromosomes in the GnomAD database, including 3 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 0.0014 (2 hom., cov: 28)
  • Exomes 𝑓: 0.00063 (1 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.1117+104_1117+107dupCCCC		intron_variant		ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.1221_1224dupCCCC	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+104_1117+107dupCCCC		intron_variant		5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1281+104_*1281+107dupCCCC		intron_variant		5		ENSP00000490901.1
CDCP2	ENST00000371330.1	c.1221_1224dupCCCC	p.Met409fs	frameshift_variant	4/4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2	n.1639_1642dupGGGG		non_coding_transcript_exon_variant	2/2	5

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 143 AN: 101544 Hom.: 2 Cov.: 28

Gnomad AFR AF: 0.0000593

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.00141

Gnomad SAS AF: 0.00221

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000429

Gnomad OTH AF: 0.00146

GnomAD3 exomes AF: 0.00152 AC: 238 AN: 156162 Hom.: 0 AF XY: 0.00168 AC XY: 143 AN XY: 85076

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000157

Gnomad ASJ exome AF: 0.0236

Gnomad EAS exome AF: 0.00131

Gnomad SAS exome AF: 0.00233

Gnomad FIN exome AF: 0.000152

Gnomad NFE exome AF: 0.000319

Gnomad OTH exome AF: 0.00190

GnomAD4 exome AF: 0.000633 AC: 906 AN: 1431454 Hom.: 1 Cov.: 59 AF XY: 0.000707 AC XY: 504 AN XY: 712422

Gnomad4 AFR exome AF: 0.0000604

Gnomad4 AMR exome AF: 0.000115

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.000846

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.0000756

Gnomad4 NFE exome AF: 0.0000836

Gnomad4 OTH exome AF: 0.00186

GnomAD4 genome AF: 0.00140 AC: 142 AN: 101664 Hom.: 2 Cov.: 28 AF XY: 0.00132 AC XY: 66 AN XY: 50160

Gnomad4 AFR AF: 0.0000591

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.0514

Gnomad4 EAS AF: 0.00142

Gnomad4 SAS AF: 0.00193

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000429

Gnomad4 OTH AF: 0.00143

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;