Variant 13-113181192-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001127202.4(PCID2):c.724C>T(p.Arg242Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,613,632 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

PCID2
NM_001127202.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.82

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4 link	c.724C>T	p.Arg242Cys	missense_variant	Exon 10 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.724C>T	p.Arg242Cys	missense_variant	Exon 10 of 14	2	NM_001127202.4	ENSP00000337405.4	Q5JVF3-1
PCID2	ENST00000375477.5 link	c.724C>T	p.Arg242Cys	missense_variant	Exon 10 of 15	1		ENSP00000364626.1	Q5JVF3-1
PCID2	ENST00000375479.6 link	c.724C>T	p.Arg242Cys	missense_variant	Exon 10 of 15	2		ENSP00000364628.2	Q5JVF3-1
PCID2	ENST00000375457.2 link	c.718C>T	p.Arg240Cys	missense_variant	Exon 10 of 14	1		ENSP00000364606.2	Q5JVF3-2
PCID2	ENST00000375459.5 link	c.718C>T	p.Arg240Cys	missense_variant	Exon 10 of 15	2		ENSP00000364608.1	Q5JVF3-2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000797

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

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251406

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135894

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461482

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000217

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000797

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

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000298

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.724C>T (p.R242C) alteration is located in exon 10 (coding exon 10) of the PCID2 gene. This alteration results from a C to T substitution at nucleotide position 724, causing the arginine (R) at amino acid position 242 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

0.11

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

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

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.042

MetaRNN

Uncertain

0.43

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

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.7

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

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-4.0

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

REVEL

Uncertain

0.42

Sift

Uncertain

0.020

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

Sift4G

Uncertain

0.047

D;D;D;D;D;D;D

Polyphen

1.0

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

Vest4

0.61

MVP

0.50

MPC

0.95

ClinPred

0.49

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.41

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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