rs4649444

Positions:

• chr1-233203465-C-A
• chr1-233203465-C-G
• chr1-233203465-C-T

Variant summary

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

The NM_014801.4(PCNX2):​c.2864-3201G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,794 control chromosomes in the GnomAD database, including 7,295 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 0.29 (7295 hom., cov: 32)
• Consequence: PCNX2 NM_014801.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNX2	NM_014801.4	c.2864-3201G>T		intron_variant		ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.2864-3201G>T		intron_variant		5	NM_014801.4	ENSP00000258229	A2

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44492 AN: 151676 Hom.: 7280 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.294 AC: 44560 AN: 151794 Hom.: 7295 Cov.: 32 AF XY: 0.296 AC XY: 21957 AN XY: 74156

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.310

Alfa AF: 0.175 Hom.: 499

Bravo AF: 0.316

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.36

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: rs4649444; hg19: chr1-233339211;