13-113200443-G-A

Position:

• chr13-113200443-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127202.4(PCID2):​c.110C>T​(p.Ala37Val) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCID2 NM_001127202.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23889396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.110C>T	p.Ala37Val	missense_variant	2/14	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.110C>T	p.Ala37Val	missense_variant	2/14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.110C>T	p.Ala37Val	missense_variant	2/15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.110C>T	p.Ala37Val	missense_variant	2/15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.104C>T	p.Ala35Val	missense_variant	2/14	1		ENSP00000364606.2
PCID2	ENST00000375459.5	c.104C>T	p.Ala35Val	missense_variant	2/15	2		ENSP00000364608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Aug 19, 2024

The c.110C>T (p.A37V) alteration is located in exon 2 (coding exon 2) of the PCID2 gene. This alteration results from a C to T substitution at nucleotide position 110, causing the alanine (A) at amino acid position 37 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	Pathogenic	0.82
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	.;T;T;T;.;.;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;.;.;D;.;.;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	1.3	L;L;L;L;.;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.5	.;N;N;N;N;N;N
REVEL	Benign	0.082
Sift	Benign	0.44	.;T;T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T;T;T
Polyphen		0.59	P;B;B;B;.;P;.
Vest4		0.35
MutPred		0.30		Loss of disorder (P = 0.0801);Loss of disorder (P = 0.0801);Loss of disorder (P = 0.0801);Loss of disorder (P = 0.0801);.;Loss of disorder (P = 0.0801);.;
MVP		0.47
MPC		0.22
ClinPred		0.81	D
GERP RS		5.5
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.10
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-113854757;