rs765951977

Variant names:

• chr13-113196209-C-G
• rs765951977
• NM_001127202.4:c.280G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-113196209-C-G
• chr13-113196209-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001127202.4(PCID2):​c.280G>C​(p.Ala94Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PCID2 NM_001127202.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.31

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.817

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.280G>C	p.Ala94Pro	missense_variant	Exon 5 of 14	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.280G>C	p.Ala94Pro	missense_variant	Exon 5 of 14	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.280G>C	p.Ala94Pro	missense_variant	Exon 5 of 15	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.280G>C	p.Ala94Pro	missense_variant	Exon 5 of 15	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.274G>C	p.Ala92Pro	missense_variant	Exon 5 of 14	1		ENSP00000364606.2
PCID2	ENST00000375459.5	c.274G>C	p.Ala92Pro	missense_variant	Exon 5 of 15	2		ENSP00000364608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251280 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135816

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;T;T;T;.;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;.;.;T;.;.;T
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.7	.;M;M;M;.;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.4	.;N;N;N;N;N;N
REVEL	Uncertain	0.38
Sift	Benign	0.23	.;T;T;T;T;D;T
Sift4G	Benign	0.13	T;T;T;T;T;T;T
Polyphen		0.91	P;P;P;P;.;P;.
Vest4		0.93
MutPred		0.60		.;Gain of methylation at K99 (P = 0.0648);Gain of methylation at K99 (P = 0.0648);Gain of methylation at K99 (P = 0.0648);.;.;.;
MVP		0.38
MPC		0.24
ClinPred		0.89	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs765951977; hg19: chr13-113850523;