13-113181168-T-C

Position:

• chr13-113181168-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001127202.4(PCID2):​c.748A>G​(p.Met250Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCID2 NM_001127202.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81

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 (HGNC:):

ACMG classification

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=0.3723905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.748A>G	p.Met250Val	missense_variant	10/14	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.748A>G	p.Met250Val	missense_variant	10/14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.748A>G	p.Met250Val	missense_variant	10/15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.748A>G	p.Met250Val	missense_variant	10/15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.742A>G	p.Met248Val	missense_variant	10/14	1		ENSP00000364606.2
PCID2	ENST00000375459.5	c.742A>G	p.Met248Val	missense_variant	10/15	2		ENSP00000364608.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.748A>G (p.M250V) alteration is located in exon 10 (coding exon 10) of the PCID2 gene. This alteration results from a A to G substitution at nucleotide position 748, causing the methionine (M) at amino acid position 250 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.25	.;T;T;T;.;.;.
Eigen	Benign	-0.038
Eigen_PC	Benign	0.10
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;.;.;D;.;.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.37	T;T;T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.3	.;M;M;M;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	.;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.018	.;D;D;D;D;D;D
Sift4G	Uncertain	0.034	D;D;D;D;D;D;D
Polyphen		0.061	B;B;B;B;.;B;.
Vest4		0.65
MutPred		0.52		.;Loss of catalytic residue at M250 (P = 0.0201);Loss of catalytic residue at M250 (P = 0.0201);Loss of catalytic residue at M250 (P = 0.0201);.;.;.;
MVP		0.23
MPC		0.68
ClinPred		0.68	D
GERP RS		4.0
Varity_R		0.54
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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

Other links and lift over

dbSNP: rs897074614; hg19: chr13-113835482;