rs777852240

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr13-113208627-T-A
• chr13-113208627-T-C
• chr13-113208627-T-G

Variant summary

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

The NM_001127202.4(PCID2):​c.8A>T​(p.His3Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• 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 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.8A>T	p.His3Leu	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>T	p.His3Leu	missense_variant	Exon 1 of 14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.8A>T	p.His3Leu	missense_variant	Exon 1 of 15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.8A>T	p.His3Leu	missense_variant	Exon 1 of 15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.-574A>T		5_prime_UTR_variant	Exon 1 of 14	1		ENSP00000364606.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.17	.;T;T;T;.
Eigen	Benign	0.19
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.88	D;.;.;D;.
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.59	D;D;D;D;D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.3	M;M;M;M;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.6	.;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.054	.;T;T;T;D
Sift4G	Benign	0.49	T;T;T;T;T
Polyphen		0.94	P;P;P;P;P
Vest4		0.61
MutPred		0.58		Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);Loss of disorder (P = 0.0172);
MVP		0.51
MPC		0.56
ClinPred		0.97	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.53
gMVP		0.64

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;