rs142022899

Variant summary

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

The NM_001127202.4(PCID2):ā€‹c.11T>Gā€‹(p.Ile4Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,607,028 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

PCID2
NM_001127202.4 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.97
Variant links:
Genes affected
PCID2 (HGNC:25653): (PCI domain containing 2) This gene encodes a component of the TREX-2 complex (transcription and export complex 2), which regulates mRNA export from the nucleus. This protein regulates expression of Mad2 mitotic arrest deficient-like 1, a cell division checkpoint protein. This protein also interacts with and stabilizes Brca2 (breast cancer 2) protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]
CUL4A (HGNC:2554): (cullin 4A) CUL4A is the ubiquitin ligase component of a multimeric complex involved in the degradation of DNA damage-response proteins (Liu et al., 2009 [PubMed 19481525]).[supplied by OMIM, Oct 2009]

Genome browser will be placed here

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=0.40846393).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PCID2NM_001127202.4 linkc.11T>G p.Ile4Ser missense_variant Exon 1 of 14 ENST00000337344.9 NP_001120674.1 Q5JVF3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PCID2ENST00000337344.9 linkc.11T>G p.Ile4Ser missense_variant Exon 1 of 14 2 NM_001127202.4 ENSP00000337405.4 Q5JVF3-1
PCID2ENST00000375477.5 linkc.11T>G p.Ile4Ser missense_variant Exon 1 of 15 1 ENSP00000364626.1 Q5JVF3-1
PCID2ENST00000375479.6 linkc.11T>G p.Ile4Ser missense_variant Exon 1 of 15 2 ENSP00000364628.2 Q5JVF3-1
PCID2ENST00000375457.2 linkc.-571T>G 5_prime_UTR_variant Exon 1 of 14 1 ENSP00000364606.2 Q5JVF3-2

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
151362
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000485
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1455666
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
723942
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
AF:
0.0000132
AC:
2
AN:
151362
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
73914
show subpopulations
Gnomad4 AFR
AF:
0.0000485
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.089
.;T;T;T;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.060
FATHMM_MKL
Benign
0.67
D
LIST_S2
Uncertain
0.91
D;.;.;D;.
M_CAP
Uncertain
0.087
D
MetaRNN
Benign
0.41
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L;L;L;L;L
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-0.60
.;N;N;N;N
REVEL
Benign
0.079
Sift
Benign
0.16
.;T;T;T;T
Sift4G
Benign
0.27
T;T;T;T;T
Polyphen
0.20
B;B;B;B;B
Vest4
0.65
MutPred
0.42
Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);Gain of disorder (P = 0.0042);
MVP
0.42
MPC
0.30
ClinPred
0.89
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.40
gMVP
0.59

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

LitVar

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

Other links and lift over

dbSNP: rs142022899; hg19: chr13-113862938; API