Variant 1-232998405-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014801.4(PCNX2):c.5637T>A(p.Ser1879Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PCNX2
NM_014801.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.81

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11642063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX2	NM_014801.4 linkuse as main transcript	c.5637T>A	p.Ser1879Arg	missense_variant	32/34	ENST00000258229.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX2	ENST00000258229.14 linkuse as main transcript	c.5637T>A	p.Ser1879Arg	missense_variant	32/34	5	NM_014801.4	A2	A6NKB5-1
PCNX2	ENST00000344698.6 linkuse as main transcript	c.1593T>A	p.Ser531Arg	missense_variant	9/10	2		P4	A6NKB5-3
PCNX2	ENST00000497623.1 linkuse as main transcript	n.557T>A		non_coding_transcript_exon_variant	2/2	2
PCNX2	ENST00000462233.5 linkuse as main transcript	c.*976T>A		3_prime_UTR_variant, NMD_transcript_variant	18/20	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460530

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Sep 14, 2021

The c.5637T>A (p.S1879R) alteration is located in exon 32 (coding exon 32) of the PCNX2 gene. This alteration results from a T to A substitution at nucleotide position 5637, causing the serine (S) at amino acid position 1879 to be replaced by an arginine (R). 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

Benign

0.20

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.075

DANN

Benign

0.97

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.8

D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.76

P;P

Vest4

0.39

MutPred

0.34

Gain of solvent accessibility (P = 1e-04);.;

MVP

0.14

MPC

0.35

ClinPred

0.62

GERP RS

-6.7

Varity_R

0.22

gMVP

0.50

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over