1-233204408-A-G

Variant names:

• chr1-233204408-A-G
• rs12027542
• NM_014801.4:c.2863+4110T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 publications found

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]

ENSG00000298828 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PCNX2	NM_014801.4	c.2863+4110T>C		intron_variant	Intron 13 of 33	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.2863+4110T>C		intron_variant	Intron 13 of 33	5	NM_014801.4	ENSP00000258229.8

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

African (AFR) AF: 0.0377 AC: 1567 AN: 41554

American (AMR) AF: 0.142 AC: 2171 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1636 AN: 5150

South Asian (SAS) AF: 0.0510 AC: 246 AN: 4826

European-Finnish (FIN) AF: 0.0688 AC: 731 AN: 10624

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0556 AC: 3783 AN: 67996

Other (OTH) AF: 0.0837 AC: 177 AN: 2114

Alfa AF: 0.0672 Hom.: 1424

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
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12027542; hg19: chr1-233340154;