rs767129015

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-113180162-C-A
• chr13-113180162-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• 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

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.856G>T	p.Val286Leu	missense_variant	Exon 11 of 14	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.856G>T	p.Val286Leu	missense_variant	Exon 11 of 14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.856G>T	p.Val286Leu	missense_variant	Exon 11 of 15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.856G>T	p.Val286Leu	missense_variant	Exon 11 of 15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.850G>T	p.Val284Leu	missense_variant	Exon 11 of 14	1		ENSP00000364606.2
PCID2	ENST00000375459.5	c.850G>T	p.Val284Leu	missense_variant	Exon 11 of 15	2		ENSP00000364608.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T;T;.;.;.
Eigen	Benign	0.070
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.97	D;.;.;D;.;.;D
M_CAP	Benign	0.034	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;L;L;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	.;N;N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	0.13	.;T;T;T;T;T;T
Sift4G	Benign	0.18	T;T;T;T;T;T;T
Polyphen		0.15	B;B;B;B;.;B;.
Vest4		0.80
MutPred		0.55		.;Gain of helix (P = 0.2684);Gain of helix (P = 0.2684);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

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

Other links and lift over

dbSNP: rs767129015; hg19: chr13-113834476;