chr1-54141250-G-A

Position:

• chr1-54141250-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001353655.3(CDCP2):​c.611C>T​(p.Ala204Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: CDCP2 NM_001353655.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.611C>T	p.Ala204Val	missense_variant	3/6	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.611C>T	p.Ala204Val	missense_variant	3/4		NP_963840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCP2	ENST00000530059.3	c.611C>T	p.Ala204Val	missense_variant	3/6	5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*775C>T		non_coding_transcript_exon_variant	7/10	5		ENSP00000490901.1
ENSG00000256407	ENST00000637610.1	n.*775C>T		3_prime_UTR_variant	7/10	5		ENSP00000490901.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 27, 2022

The c.611C>T (p.A204V) alteration is located in exon 3 (coding exon 3) of the CDCP2 gene. This alteration results from a C to T substitution at nucleotide position 611, causing the alanine (A) at amino acid position 204 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.023	.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.9	.;N
REVEL	Benign	0.11
Sift	Uncertain	0.021	.;D
Sift4G	Benign	0.13	.;T
Polyphen		0.89	.;P
Vest4		0.35
MutPred		0.54		Loss of disorder (P = 0.1671);Loss of disorder (P = 0.1671);
MVP		0.41
MPC		0.14
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.30
gMVP		0.48

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-54606923;