1-54139980-A-C

Variant names:

• chr1-54139980-A-C
• NM_001353655.3:c.890T>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001353655.3(CDCP2):​c.890T>G​(p.Val297Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDCP2 NM_001353655.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.15

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.890T>G	p.Val297Gly	missense_variant	Exon 4 of 6	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.890T>G	p.Val297Gly	missense_variant	Exon 4 of 4		NP_963840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDCP2	ENST00000530059.3	c.890T>G	p.Val297Gly	missense_variant	Exon 4 of 6	5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1054T>G		non_coding_transcript_exon_variant	Exon 8 of 10	5		ENSP00000490901.1
ENSG00000256407	ENST00000637610.1	n.*1054T>G		3_prime_UTR_variant	Exon 8 of 10	5		ENSP00000490901.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.890T>G (p.V297G) alteration is located in exon 4 (coding exon 4) of the CDCP2 gene. This alteration results from a T to G substitution at nucleotide position 890, causing the valine (V) at amino acid position 297 to be replaced by a glycine (G). 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	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.031	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-5.9	.;D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	.;D
Sift4G	Uncertain	0.0020	.;D
Polyphen		1.0	.;D
Vest4		0.69
MutPred		0.67		Loss of stability (P = 0.0232);Loss of stability (P = 0.0232);
MVP		0.30
MPC		0.31
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.89
gMVP		0.84

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: chr1-54605653;