Variant 13-113181188-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001127202.4(PCID2):c.728C>G(p.Ser243Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCID2
NM_001127202.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

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:

PCID2 (HGNC:):

PCID2 links:

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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=0.32678944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCID2	NM_001127202.4 linkuse as main transcript	c.728C>G	p.Ser243Cys	missense_variant	10/14	ENST00000337344.9	NP_001120674.1	Q5JVF3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCID2	ENST00000337344.9 linkuse as main transcript	c.728C>G	p.Ser243Cys	missense_variant	10/14	2	NM_001127202.4	ENSP00000337405.4	Q5JVF3-1
PCID2	ENST00000375477.5 linkuse as main transcript	c.728C>G	p.Ser243Cys	missense_variant	10/15	1		ENSP00000364626.1	Q5JVF3-1
PCID2	ENST00000375479.6 linkuse as main transcript	c.728C>G	p.Ser243Cys	missense_variant	10/15	2		ENSP00000364628.2	Q5JVF3-1
PCID2	ENST00000375457.2 linkuse as main transcript	c.722C>G	p.Ser241Cys	missense_variant	10/14	1		ENSP00000364606.2	Q5JVF3-2
PCID2	ENST00000375459.5 linkuse as main transcript	c.722C>G	p.Ser241Cys	missense_variant	10/15	2		ENSP00000364608.1	Q5JVF3-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

6.84e-7

AC:

AN:

1461546

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.728C>G (p.S243C) alteration is located in exon 10 (coding exon 10) of the PCID2 gene. This alteration results from a C to G substitution at nucleotide position 728, causing the serine (S) at amino acid position 243 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.57

.;D;D;D;.;.;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.43

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.95

D;.;.;D;.;.;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.33

T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

2.0

.;M;M;M;.;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Uncertain

-3.1

.;D;D;D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.020

.;D;D;D;D;D;D

Sift4G

Uncertain

0.050

T;D;D;D;D;T;D

Polyphen

0.98

D;P;P;P;.;D;.

Vest4

0.44

MutPred

0.36

.;Loss of disorder (P = 9e-04);Loss of disorder (P = 9e-04);Loss of disorder (P = 9e-04);.;.;.;

MVP

0.33

MPC

1.3

ClinPred

0.76

GERP RS

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.27

gMVP

0.29

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over