dbSNP rs201981443: PCID2:p.Cys83Phe (chr13-113197196-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001127202.4(PCID2):c.248G>T(p.Cys83Phe) 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 1,461,826 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCID2
NM_001127202.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.14

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17933324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4 link	c.248G>T	p.Cys83Phe	missense_variant	Exon 4 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.248G>T	p.Cys83Phe	missense_variant	Exon 4 of 14	2	NM_001127202.4	ENSP00000337405.4	Q5JVF3-1
PCID2	ENST00000375477.5 link	c.248G>T	p.Cys83Phe	missense_variant	Exon 4 of 15	1		ENSP00000364626.1	Q5JVF3-1
PCID2	ENST00000375479.6 link	c.248G>T	p.Cys83Phe	missense_variant	Exon 4 of 15	2		ENSP00000364628.2	Q5JVF3-1
PCID2	ENST00000375457.2 link	c.242G>T	p.Cys81Phe	missense_variant	Exon 4 of 14	1		ENSP00000364606.2	Q5JVF3-2
PCID2	ENST00000375459.5 link	c.242G>T	p.Cys81Phe	missense_variant	Exon 4 of 15	2		ENSP00000364608.1	Q5JVF3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Uncertain

0.54

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

Eigen

Benign

-0.16

Eigen_PC

Benign

0.021

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.0020

MetaRNN

Benign

0.18

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.2

L;L;L;L;.;L;.

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.6

.;D;D;D;D;N;D

REVEL

Benign

0.081

Sift

Benign

0.68

.;T;T;T;T;T;T

Sift4G

Benign

0.69

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

Polyphen

0.0090

B;B;B;B;.;B;.

Vest4

0.31

MutPred

0.34

Loss of methylation at K82 (P = 0.0335);Loss of methylation at K82 (P = 0.0335);Loss of methylation at K82 (P = 0.0335);Loss of methylation at K82 (P = 0.0335);.;Loss of methylation at K82 (P = 0.0335);.;

MVP

0.51

MPC

0.27

ClinPred

0.69

GERP RS

5.0

Varity_R

0.27

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over