13-113196211-C-A

Variant names:

• chr13-113196211-C-A
• NM_001127202.4:c.278G>T

Variant summary

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

The NM_001127202.4(PCID2):​c.278G>T​(p.Arg93Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,902 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PCID2 NM_001127202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.278G>T	p.Arg93Leu	missense_variant	Exon 5 of 14	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.278G>T	p.Arg93Leu	missense_variant	Exon 5 of 14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.278G>T	p.Arg93Leu	missense_variant	Exon 5 of 15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.278G>T	p.Arg93Leu	missense_variant	Exon 5 of 15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.272G>T	p.Arg91Leu	missense_variant	Exon 5 of 14	1		ENSP00000364606.2
PCID2	ENST00000375459.5	c.272G>T	p.Arg91Leu	missense_variant	Exon 5 of 15	2		ENSP00000364608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448902 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 720792

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: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	.;D;D;D;.;.;.
Eigen	Benign	0.051
Eigen_PC	Benign	0.14
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;.;.;T;.;.;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.49	T;T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
MutationAssessor	Uncertain	2.2	.;M;M;M;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.3	.;D;D;D;D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0040	.;D;D;D;D;D;D
Sift4G	Uncertain	0.0060	D;D;D;D;D;D;D
Polyphen		0.48	P;B;B;B;.;P;.
Vest4		0.70
MutPred		0.52		.;Loss of catalytic residue at R93 (P = 0.1165);Loss of catalytic residue at R93 (P = 0.1165);Loss of catalytic residue at R93 (P = 0.1165);.;.;.;
MVP		0.36
MPC		0.23
ClinPred		0.98	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: -3

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: chr13-113850525;