dbSNP rs142022899: PCID2:p.Ile4Ser (chr13-113208624-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_001127202.4(PCID2):c.11T>G(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: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCID2
NM_001127202.4 missense

Scores

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]

PCID2 links:

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]

CUL4A links:

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
PCID2	NM_001127202.4 link	c.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	UniProt
PCID2	ENST00000337344.9 link	c.11T>G	p.Ile4Ser	missense_variant	Exon 1 of 14	2	NM_001127202.4	ENSP00000337405.4	Q5JVF3-1
PCID2	ENST00000375477.5 link	c.11T>G	p.Ile4Ser	missense_variant	Exon 1 of 15	1		ENSP00000364626.1	Q5JVF3-1
PCID2	ENST00000375479.6 link	c.11T>G	p.Ile4Ser	missense_variant	Exon 1 of 15	2		ENSP00000364628.2	Q5JVF3-1
PCID2	ENST00000375457.2 link	c.-571T>G		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000364606.2	Q5JVF3-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151362

Hom.:

Cov.:

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:

AN:

1455666

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

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:

AN:

151362

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

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

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

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

LIST_S2

Uncertain

0.91

D;.;.;D;.

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.41

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;L;L

PrimateAI

Pathogenic

0.80

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over