chr13-113208627-T-C

Variant names:

• chr13-113208627-T-C
• rs777852240
• NM_001127202.4:c.8A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001127202.4(PCID2):​c.8A>G​(p.His3Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,455,910 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: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PCID2 NM_001127202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.77

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34972417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.8A>G	p.His3Arg	missense_variant	Exon 1 of 14	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.8A>G	p.His3Arg	missense_variant	Exon 1 of 14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.8A>G	p.His3Arg	missense_variant	Exon 1 of 15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.8A>G	p.His3Arg	missense_variant	Exon 1 of 15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.-574A>G		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000364606.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000847 AC: 2 AN: 236218 Hom.: 0 AF XY: 0.00000774 AC XY: 1 AN XY: 129280

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad SAS exome AF: 0.0000335

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1455910 Hom.: 0 Cov.: 33 AF XY: 0.00000414 AC XY: 3 AN XY: 724050

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000507

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.0000166 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;T;T;T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.91	D;.;.;D;.
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-0.45	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.7	.;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.10	.;T;T;T;T
Sift4G	Benign	0.37	T;T;T;T;T
Polyphen		0.98	D;P;P;P;D
Vest4		0.47
MutPred		0.53		Gain of MoRF binding (P = 0.0012);Gain of MoRF binding (P = 0.0012);Gain of MoRF binding (P = 0.0012);Gain of MoRF binding (P = 0.0012);Gain of MoRF binding (P = 0.0012);
MVP		0.44
MPC		0.51
ClinPred		0.85	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.50
gMVP		0.54

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: rs777852240; hg19: chr13-113862941;