1-54139569-G-T

Variant names:

• chr1-54139569-G-T
• rs41294792
• NM_001353655.3:c.1117+184C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_201546.5(CDCP2):​c.1301C>A​(p.Thr434Lys) 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. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T434M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDCP2 NM_201546.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 3 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: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201546.5. 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.1117+184C>A		intron	N/A	NP_001340584.1	Q5VXM1-3
	CDCP2	NM_201546.5		c.1301C>A	p.Thr434Lys	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.1117+184C>A		intron	N/A	ENSP00000489959.1	Q5VXM1-3
	ENSG00000256407	ENST00000637610.1	TSL:5	n.*1281+184C>A		intron	N/A	ENSP00000490901.1	A0A1B0GWF0
	CDCP2	ENST00000371330.1	TSL:2	c.1301C>A	p.Thr434Lys	missense	Exon 4 of 4	ENSP00000360381.1	Q5VXM1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.025
DANN	Benign	0.70
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.0030
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.078	T
Polyphen		0.012	B
Vest4		0.13
MutPred		0.46		Gain of ubiquitination at T434 (P = 0.0114)
MVP		0.067
MPC		0.057
ClinPred		0.078	T
GERP RS		-4.8
Varity_R		0.094
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41294792; hg19: chr1-54605242;