Genetic Variant PCID2:p.Ala94Pro (chr13-113196209-C-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001127202.4(PCID2):c.280G>C(p.Ala94Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A94T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PCID2
NM_001127202.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.31

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.817

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127202.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCID2	NM_001127202.4	MANE Select	c.280G>C	p.Ala94Pro	missense	Exon 5 of 14	NP_001120674.1	Q5JVF3-1
PCID2	NM_001320656.2		c.442G>C	p.Ala148Pro	missense	Exon 5 of 15	NP_001307585.1	Q5JVF3-4
PCID2	NM_001320657.2		c.280G>C	p.Ala94Pro	missense	Exon 5 of 14	NP_001307586.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCID2	ENST00000337344.9	TSL:2 MANE Select	c.280G>C	p.Ala94Pro	missense	Exon 5 of 14	ENSP00000337405.4	Q5JVF3-1
PCID2	ENST00000375477.5	TSL:1	c.280G>C	p.Ala94Pro	missense	Exon 5 of 15	ENSP00000364626.1	Q5JVF3-1
PCID2	ENST00000375479.6	TSL:2	c.280G>C	p.Ala94Pro	missense	Exon 5 of 15	ENSP00000364628.2	Q5JVF3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251280

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.016

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.7

PhyloP100

7.3

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.38

Sift

Benign

0.23

Sift4G

Benign

0.13

Polyphen

0.91

Vest4

0.93

MutPred

0.60

Gain of methylation at K99 (P = 0.0648)

MVP

0.38

MPC

0.24

ClinPred

0.89

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.78

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over