rs12027542

Positions:

• chr1-233204408-A-G
• chr1-233204408-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014801.4(PCNX2):​c.2863+4110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0696 in 152,232 control chromosomes in the GnomAD database, including 620 homozygotes. 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: 𝑓 0.070 (620 hom., cov: 32)
• Consequence: PCNX2 NM_014801.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.707

Genes affected

PCNX2 (HGNC:8736): (pecanex 2) This gene contains coding mononucleotide repeats that are associated with tumors of high mcrosatellite instability (MSI-H). Defects in this gene are involved in the tumorigenesis of MSI-H colorectal carcinomas. [provided by RefSeq, Jun 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX2	NM_014801.4	c.2863+4110T>C		intron_variant		ENST00000258229.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX2	ENST00000258229.14	c.2863+4110T>C		intron_variant		5	NM_014801.4	A2

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10587 AN: 152114 Hom.: 621 Cov.: 32

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.0841

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0696 AC: 10601 AN: 152232 Hom.: 620 Cov.: 32 AF XY: 0.0726 AC XY: 5403 AN XY: 74426

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.0545

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.0510

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.0556

Gnomad4 OTH AF: 0.0837

Alfa AF: 0.0666 Hom.: 740

Bravo AF: 0.0780

Asia WGS AF: 0.164 AC: 570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.47

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: rs12027542; hg19: chr1-233340154;