chr1-54140007-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001353655.3(CDCP2):​c.863G>T​(p.Arg288Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. R288C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CDCP2
NM_001353655.3 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34533796).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDCP2NM_001353655.3 linkc.863G>T p.Arg288Leu missense_variant Exon 4 of 6 ENST00000530059.3 NP_001340584.1
CDCP2NM_201546.5 linkc.863G>T p.Arg288Leu missense_variant Exon 4 of 4 NP_963840.2 Q5VXM1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDCP2ENST00000530059.3 linkc.863G>T p.Arg288Leu missense_variant Exon 4 of 6 5 NM_001353655.3 ENSP00000489959.1 A0A1B0GU47
ENSG00000256407ENST00000637610.1 linkn.*1027G>T non_coding_transcript_exon_variant Exon 8 of 10 5 ENSP00000490901.1 A0A1B0GWF0
ENSG00000256407ENST00000637610.1 linkn.*1027G>T 3_prime_UTR_variant Exon 8 of 10 5 ENSP00000490901.1 A0A1B0GWF0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461726
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
727164
show subpopulations
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.029
.;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.39
FATHMM_MKL
Uncertain
0.88
D
LIST_S2
Uncertain
0.86
D;D
M_CAP
Benign
0.0091
T
MetaRNN
Benign
0.35
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
.;L
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-2.0
.;N
REVEL
Benign
0.14
Sift
Benign
0.54
.;T
Sift4G
Uncertain
0.059
.;T
Polyphen
0.87
.;P
Vest4
0.39
MutPred
0.63
Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);
MVP
0.40
MPC
0.18
ClinPred
0.93
D
GERP RS
4.7
Varity_R
0.14
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149009344; hg19: chr1-54605680; API