13-113190938-A-G

Variant names:

• chr13-113190938-A-G
• NM_001127202.4:c.401T>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001353095.2(PCID2):​c.-2181T>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000684 in 1,461,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PCID2 NM_001353095.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• 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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06659788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.401T>C	p.Val134Ala	missense_variant	Exon 7 of 14	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.401T>C	p.Val134Ala	missense_variant	Exon 7 of 14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.401T>C	p.Val134Ala	missense_variant	Exon 7 of 15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.401T>C	p.Val134Ala	missense_variant	Exon 7 of 15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.395T>C	p.Val132Ala	missense_variant	Exon 7 of 14	1		ENSP00000364606.2
PCID2	ENST00000375459.5	c.395T>C	p.Val132Ala	missense_variant	Exon 7 of 15	2		ENSP00000364608.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461298 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726978

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.60
DEOGEN2	Benign	0.075	.;T;T;T;.;.;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T;.;.;T;.;.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.067	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	.;N;N;N;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.49	.;N;N;N;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.90	.;T;T;T;T;T;T
Sift4G	Benign	0.88	T;T;T;T;T;T;T
Polyphen		0.012	B;B;B;B;.;B;.
Vest4		0.21
MutPred		0.34		.;Loss of stability (P = 0.0323);Loss of stability (P = 0.0323);Loss of stability (P = 0.0323);.;.;.;
MVP		0.24
MPC		1.9
ClinPred		0.27	T
GERP RS		4.4
Varity_R		0.021
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-113845252;