chr1-54139643-C-T

Variant names:

• chr1-54139643-C-T
• NM_001353655.3:c.1117+110G>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.1227G>A​(p.Met409Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CDCP2 NM_201546.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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=0.07792476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDCP2	NM_001353655.3	c.1117+110G>A		intron_variant	Intron 4 of 5	ENST00000530059.3	NP_001340584.1
CDCP2	NM_201546.5	c.1227G>A	p.Met409Ile	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+110G>A		intron_variant	Intron 4 of 5	5	NM_001353655.3	ENSP00000489959.1
ENSG00000256407	ENST00000637610.1	n.*1281+110G>A		intron_variant	Intron 8 of 9	5		ENSP00000490901.1
CDCP2	ENST00000371330.1	c.1227G>A	p.Met409Ile	missense_variant	Exon 4 of 4	2		ENSP00000360381.1
ENSG00000280425	ENST00000623663.2	n.1632C>T		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1436532 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 714514

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.85
DANN	Benign	0.82
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.26	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.078	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.019
Sift	Benign	0.033	D
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.089
MutPred		0.27		Loss of glycosylation at P408 (P = 0.0747);
MVP		0.19
MPC		0.054
ClinPred		0.20	T
GERP RS		-0.30
Varity_R		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-54605316;