13-113180162-C-A

Variant names:

• chr13-113180162-C-A
• rs767129015
• NM_001127202.4:c.856G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001127202.4(PCID2):​c.856G>T​(p.Val286Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V286M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PCID2 NM_001127202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.52
• Publications: 0 publications found

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]

ACMG classification

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, 0.797

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCID2	NM_001127202.4	MANE Select	c.856G>T	p.Val286Leu	missense	Exon 11 of 14	NP_001120674.1	Q5JVF3-1
	PCID2	NM_001320656.2		c.1018G>T	p.Val340Leu	missense	Exon 11 of 15	NP_001307585.1	Q5JVF3-4
	PCID2	NM_001320657.2		c.856G>T	p.Val286Leu	missense	Exon 11 of 14	NP_001307586.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCID2	ENST00000337344.9	TSL:2 MANE Select	c.856G>T	p.Val286Leu	missense	Exon 11 of 14	ENSP00000337405.4	Q5JVF3-1
	PCID2	ENST00000375477.5	TSL:1	c.856G>T	p.Val286Leu	missense	Exon 11 of 15	ENSP00000364626.1	Q5JVF3-1
	PCID2	ENST00000375479.6	TSL:2	c.856G>T	p.Val286Leu	missense	Exon 11 of 15	ENSP00000364628.2	Q5JVF3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461678 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727168

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111822

Other (OTH) AF: 0.0000166 AC: 1 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.86
BayesDel_addAF	Benign	0.0053	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.070
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		7.5
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.17
Sift	Benign	0.13	T
Sift4G	Benign	0.18	T
Polyphen		0.15	B
Vest4		0.80
MutPred		0.55		Gain of helix (P = 0.2684)
MVP		0.19
MPC		1.2
ClinPred		0.76	D
GERP RS		5.8
Varity_R		0.52
gMVP		0.70
Mutation Taster		=19/81	disease causing

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

Other links and lift over

dbSNP: rs767129015; hg19: chr13-113834476;