chr1-54139899-C-T

Position:

• chr1-54139899-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001353655.3(CDCP2):​c.971G>A​(p.Gly324Glu) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 7.56

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.971G>A	p.Gly324Glu	missense_variant	4/6	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.971G>A	p.Gly324Glu	missense_variant	4/4		NP_963840.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDCP2	ENST00000530059.3	c.971G>A	p.Gly324Glu	missense_variant	4/6	5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1135G>A		non_coding_transcript_exon_variant	8/10	5		ENSP00000490901.1
ENSG00000256407	ENST00000637610.1	n.*1135G>A		3_prime_UTR_variant	8/10	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.971G>A (p.G324E) alteration is located in exon 4 (coding exon 4) of the CDCP2 gene. This alteration results from a G to A substitution at nucleotide position 971, causing the glycine (G) at amino acid position 324 to be replaced by a glutamic acid (E). 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	0.91
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.8	.;M
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-7.7	.;D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	.;D
Sift4G	Pathogenic	0.0	.;D
Polyphen		1.0	.;D
Vest4		0.91
MutPred		0.79		Gain of disorder (P = 0.0528);Gain of disorder (P = 0.0528);
MVP		0.40
MPC		0.37
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.91
gMVP		0.94

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: chr1-54605572;