1-54139743-C-T

Variant names:

• chr1-54139743-C-T
• NM_001353655.3:c.1117+10G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_201546.5(CDCP2):​c.1127G>A​(p.Gly376Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDCP2 NM_201546.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16308263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.1117+10G>A		intron_variant	Intron 4 of 5	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.1127G>A	p.Gly376Asp	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.1117+10G>A		intron_variant	Intron 4 of 5	5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1281+10G>A		intron_variant	Intron 8 of 9	5		ENSP00000490901.1
CDCP2	ENST00000371330.1	c.1127G>A	p.Gly376Asp	missense_variant	Exon 4 of 4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2	n.1732C>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

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 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1127G>A (p.G376D) 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 1127, causing the glycine (G) at amino acid position 376 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.6
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.045
Eigen_PC	Benign	-0.0075
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.095
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.044	D
Polyphen		0.84	P
Vest4		0.27
MutPred		0.30		Loss of sheet (P = 0.0054);
MVP		0.29
MPC		0.34
ClinPred		0.71	D
GERP RS		3.4
Varity_R		0.097

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: chr1-54605416;