1-233248365-T-G

Variant names:

• chr1-233248365-T-G
• rs965917
• NM_014801.4:c.2222+2374A>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.2222+2374A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 151,682 control chromosomes in the GnomAD database, including 41,637 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 0.74 (41637 hom., cov: 28)
• Consequence: PCNX2 NM_014801.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX2	NM_014801.4	c.2222+2374A>C		intron_variant	Intron 8 of 33	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.2222+2374A>C		intron_variant	Intron 8 of 33	5	NM_014801.4	ENSP00000258229.8
PCNX2	ENST00000475463.6	n.512+2374A>C		intron_variant	Intron 4 of 16	1		ENSP00000429360.1
PCNX2	ENST00000324142.4	n.428+2374A>C		intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes AF: 0.740 AC: 112182 AN: 151566 Hom.: 41608 Cov.: 28

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.740 AC: 112264 AN: 151682 Hom.: 41637 Cov.: 28 AF XY: 0.736 AC XY: 54546 AN XY: 74080

African (AFR) AF: 0.747 AC: 30894 AN: 41330

American (AMR) AF: 0.748 AC: 11408 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2738 AN: 3472

East Asian (EAS) AF: 0.668 AC: 3428 AN: 5134

South Asian (SAS) AF: 0.597 AC: 2857 AN: 4786

European-Finnish (FIN) AF: 0.735 AC: 7733 AN: 10526

Middle Eastern (MID) AF: 0.757 AC: 221 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50717 AN: 67884

Other (OTH) AF: 0.754 AC: 1575 AN: 2088

Alfa AF: 0.740 Hom.: 31841

Bravo AF: 0.745

Asia WGS AF: 0.628 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.76
PhyloP100		-0.11
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: rs965917; hg19: chr1-233384111; COSMIC: COSV50788573;