1-233035533-G-C

Variant names:

• chr1-233035533-G-C
• rs6424268
• NM_014801.4:c.4352-10134C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014801.4(PCNX2):​c.4352-10134C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,100 control chromosomes in the GnomAD database, including 7,496 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 0.27 (7496 hom., cov: 32)
• Consequence: PCNX2 NM_014801.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.260
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX2	NM_014801.4	c.4352-10134C>G		intron_variant	Intron 25 of 33	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14	c.4352-10134C>G		intron_variant	Intron 25 of 33	5	NM_014801.4	ENSP00000258229.8
PCNX2	ENST00000344698.6	c.308-10134C>G		intron_variant	Intron 2 of 9	2		ENSP00000340759.2
PCNX2	ENST00000429988.2	n.423-10134C>G		intron_variant	Intron 1 of 1	4
PCNX2	ENST00000462233.5	n.1415-18379C>G		intron_variant	Intron 12 of 19	2		ENSP00000428488.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41148 AN: 151980 Hom.: 7476 Cov.: 32

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.294

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

GnomAD4 genome AF: 0.271 AC: 41211 AN: 152100 Hom.: 7496 Cov.: 32 AF XY: 0.264 AC XY: 19626 AN XY: 74360

African (AFR) AF: 0.519 AC: 21515 AN: 41452

American (AMR) AF: 0.172 AC: 2622 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1417 AN: 5156

South Asian (SAS) AF: 0.138 AC: 665 AN: 4820

European-Finnish (FIN) AF: 0.122 AC: 1291 AN: 10602

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.180 AC: 12253 AN: 67996

Other (OTH) AF: 0.296 AC: 625 AN: 2112

Alfa AF: 0.0937 Hom.: 116

Bravo AF: 0.288

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.9
DANN	Benign	0.43
PhyloP100		0.26
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: rs6424268; hg19: chr1-233171279;