Variant 13-113208627-T-G 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.8A>C(p.His3Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000687 in 1,455,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

PCID2
NM_001127202.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.77

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=0.39934438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4 link	c.8A>C	p.His3Pro	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.8A>C	p.His3Pro	missense_variant	Exon 1 of 14	2	NM_001127202.4	ENSP00000337405.4	Q5JVF3-1
PCID2	ENST00000375477.5 link	c.8A>C	p.His3Pro	missense_variant	Exon 1 of 15	1		ENSP00000364626.1	Q5JVF3-1
PCID2	ENST00000375479.6 link	c.8A>C	p.His3Pro	missense_variant	Exon 1 of 15	2		ENSP00000364628.2	Q5JVF3-1
PCID2	ENST00000375457.2 link	c.-574A>C		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000364606.2	Q5JVF3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000212

AC:

AN:

236218

Hom.:

AF XY:

0.0000155

AC XY:

AN XY:

129280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000168

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000687

AC:

AN:

1455912

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

724050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000451

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000301

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000831

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8A>C (p.H3P) alteration is located in exon 1 (coding exon 1) of the PCID2 gene. This alteration results from a A to C substitution at nucleotide position 8, causing the histidine (H) at amino acid position 3 to be replaced by a proline (P). 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

Pathogenic

0.65

BayesDel_addAF

Benign

-0.080

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.25

.;T;T;T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.0033

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.88

D;.;.;D;.

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.40

T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.7

L;L;L;L;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.9

.;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.25

.;T;T;T;T

Sift4G

Benign

0.37

T;T;T;T;T

Polyphen

0.084

B;B;B;B;B

Vest4

0.62

MutPred

0.52

Gain of catalytic residue at H3 (P = 0.0265);Gain of catalytic residue at H3 (P = 0.0265);Gain of catalytic residue at H3 (P = 0.0265);Gain of catalytic residue at H3 (P = 0.0265);Gain of catalytic residue at H3 (P = 0.0265);

MVP

0.43

MPC

0.29

ClinPred

0.54

GERP RS

4.5

Varity_R

0.62

gMVP

0.68

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