chr13-113190938-A-G

Variant names:

• chr13-113190938-A-G
• rs1250516926
• NM_001127202.4:c.401T>C

Variant summary

Our verdict is Likely benign. The variant received -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
• 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: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353095.2. 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.401T>C	p.Val134Ala	missense	Exon 7 of 14	NP_001120674.1	Q5JVF3-1
	PCID2	NM_001353095.2		c.-2181T>C		5_prime_UTR_premature_start_codon_gain	Exon 7 of 15	NP_001340024.1
	PCID2	NM_001320656.2		c.563T>C	p.Val188Ala	missense	Exon 7 of 15	NP_001307585.1	Q5JVF3-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCID2	ENST00000337344.9	TSL:2 MANE Select	c.401T>C	p.Val134Ala	missense	Exon 7 of 14	ENSP00000337405.4	Q5JVF3-1
	PCID2	ENST00000375477.5	TSL:1	c.401T>C	p.Val134Ala	missense	Exon 7 of 15	ENSP00000364626.1	Q5JVF3-1
	PCID2	ENST00000375479.6	TSL:2	c.401T>C	p.Val134Ala	missense	Exon 7 of 15	ENSP00000364628.2	Q5JVF3-1

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

African (AFR) AF: 0.00 AC: 0 AN: 33428

American (AMR) AF: 0.0000224 AC: 1 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111690

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		6.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.059
Sift	Benign	0.90	T
Sift4G	Benign	0.88	T
Polyphen		0.012	B
Vest4		0.21
MutPred		0.34		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
Mutation Taster		=78/22	polymorphism

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: rs1250516926; hg19: chr13-113845252;