Variant chr1-233200215-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014801.4(PCNX2):c.2913A>C(p.Gln971His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000778 in 1,594,456 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

PCNX2
NM_014801.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

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]

PCNX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX2	NM_014801.4 linkuse as main transcript	c.2913A>C	p.Gln971His	missense_variant	14/34	ENST00000258229.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX2	ENST00000258229.14 linkuse as main transcript	c.2913A>C	p.Gln971His	missense_variant	14/34	5	NM_014801.4	A2	A6NKB5-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000127

AC:

AN:

220040

Hom.:

AF XY:

0.000110

AC XY:

AN XY:

118016

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000322

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000348

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.000359

GnomAD4 exome

AF:

0.0000811

AC:

117

AN:

1442372

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

715328

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000240

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000420

Gnomad4 NFE exome

AF:

0.0000844

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000711

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000191

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.2913A>C (p.Q971H) alteration is located in exon 14 (coding exon 14) of the PCNX2 gene. This alteration results from a A to C substitution at nucleotide position 2913, causing the glutamine (Q) at amino acid position 971 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;.;.;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.83

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Uncertain

-0.064

MutationAssessor

Pathogenic

3.1

M;.;.;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Pathogenic

-4.7

D;D;.;D

REVEL

Uncertain

0.56

Sift

Uncertain

0.0010

D;D;.;D

Sift4G

Uncertain

0.0020

D;D;D;.

Polyphen

1.0

D;.;.;.

Vest4

0.94

MutPred

0.26

Loss of loop (P = 0.2897);.;.;.;

MVP

0.84

MPC

0.62

ClinPred

0.54

GERP RS

2.2

Varity_R

0.42

gMVP

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over