1-54139864-A-G

Variant names:

• chr1-54139864-A-G
• NM_001353655.3:c.1006T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001353655.3(CDCP2):​c.1006T>C​(p.Cys336Arg) 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C336Y) has been classified 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: 8.94
• Publications: 0 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.985

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCP2	NM_001353655.3	MANE Select	c.1006T>C	p.Cys336Arg	missense	Exon 4 of 6	NP_001340584.1	Q5VXM1-3
	CDCP2	NM_201546.5		c.1006T>C	p.Cys336Arg	missense	Exon 4 of 4	NP_963840.2	Q5VXM1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDCP2	ENST00000530059.3	TSL:5 MANE Select	c.1006T>C	p.Cys336Arg	missense	Exon 4 of 6	ENSP00000489959.1	Q5VXM1-3
	ENSG00000256407	ENST00000637610.1	TSL:5	n.*1170T>C		non_coding_transcript_exon	Exon 8 of 10	ENSP00000490901.1	A0A1B0GWF0
	ENSG00000256407	ENST00000637610.1	TSL:5	n.*1170T>C		3_prime_UTR	Exon 8 of 10	ENSP00000490901.1	A0A1B0GWF0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.94
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.048	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	3.6	H
PhyloP100		8.9
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-12	D
REVEL	Pathogenic	0.77
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.94
MutPred		0.94		Gain of disorder (P = 0.0243)
MVP		0.47
MPC		0.43
ClinPred		1.0	D
GERP RS		5.8
Varity_R		0.97
gMVP		0.93
Mutation Taster		=10/90	disease causing

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

Other links and lift over

hg19: chr1-54605537;