rs200040694

Variant names:

• chr13-113178291-C-A
• rs200040694
• NM_001127202.4:c.1111-4G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-113178291-C-A
• chr13-113178291-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127202.4(PCID2):​c.1111-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000549 in 1,458,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: PCID2 NM_001127202.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001308
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCID2	NM_001127202.4	c.1111-4G>T		splice_region_variant, intron_variant	Intron 13 of 13	ENST00000337344.9	NP_001120674.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCID2	ENST00000337344.9	c.1111-4G>T		splice_region_variant, intron_variant	Intron 13 of 13	2	NM_001127202.4	ENSP00000337405.4
PCID2	ENST00000375477.5	c.1111-4G>T		splice_region_variant, intron_variant	Intron 13 of 14	1		ENSP00000364626.1
PCID2	ENST00000375479.6	c.1111-4G>T		splice_region_variant, intron_variant	Intron 13 of 14	2		ENSP00000364628.2
PCID2	ENST00000375457.2	c.1105-4G>T		splice_region_variant, intron_variant	Intron 13 of 13	1		ENSP00000364606.2
PCID2	ENST00000375459.5	c.1105-4G>T		splice_region_variant, intron_variant	Intron 13 of 14	2		ENSP00000364608.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000549 AC: 8 AN: 1458124 Hom.: 0 Cov.: 28 AF XY: 0.00000689 AC XY: 5 AN XY: 725656

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000721

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.089
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000013
dbscSNV1_RF	Benign	0.0060
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: rs200040694; hg19: chr13-113832605;