13-113208624-A-C

Variant names:

• chr13-113208624-A-C
• rs142022899
• NM_001127202.4:c.11T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001127202.4(PCID2):​c.11T>G​(p.Ile4Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,607,028 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I4T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PCID2 NM_001127202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.97
• Publications: 1 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]

CUL4A (HGNC:2554): (cullin 4A) CUL4A is the ubiquitin ligase component of a multimeric complex involved in the degradation of DNA damage-response proteins (Liu et al., 2009 [PubMed 19481525]).[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40846393).

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.11T>G	p.Ile4Ser	missense	Exon 1 of 14	NP_001120674.1	Q5JVF3-1
	PCID2	NM_001320656.2		c.11T>G	p.Ile4Ser	missense	Exon 1 of 15	NP_001307585.1	Q5JVF3-4
	PCID2	NM_001320657.2		c.11T>G	p.Ile4Ser	missense	Exon 1 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.11T>G	p.Ile4Ser	missense	Exon 1 of 14	ENSP00000337405.4	Q5JVF3-1
	PCID2	ENST00000375477.5	TSL:1	c.11T>G	p.Ile4Ser	missense	Exon 1 of 15	ENSP00000364626.1	Q5JVF3-1
	PCID2	ENST00000375479.6	TSL:2	c.11T>G	p.Ile4Ser	missense	Exon 1 of 15	ENSP00000364628.2	Q5JVF3-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151362 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455666 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723942

African (AFR) AF: 0.00 AC: 0 AN: 33178

American (AMR) AF: 0.00 AC: 0 AN: 44358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39422

South Asian (SAS) AF: 0.00 AC: 0 AN: 85618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109694

Other (OTH) AF: 0.00 AC: 0 AN: 60042

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151362 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73914

African (AFR) AF: 0.0000485 AC: 2 AN: 41254

American (AMR) AF: 0.00 AC: 0 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5002

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67738

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.78
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.089	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.087	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.0
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.079
Sift	Benign	0.16	T
Sift4G	Benign	0.27	T
Polyphen		0.20	B
Vest4		0.65
MutPred		0.42		Gain of disorder (P = 0.0042)
MVP		0.42
MPC		0.30
ClinPred		0.89	D
GERP RS		4.5
PromoterAI		0.041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.40
gMVP		0.59
Mutation Taster		=64/36	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: rs142022899; hg19: chr13-113862938;