Variant chr1-232986152-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014801.4(PCNX2):c.6180A>T(p.Ser2060=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,570,334 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 22 hom. )

Consequence

PCNX2
NM_014801.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.18

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-232986152-T-A is Benign according to our data. Variant chr1-232986152-T-A is described in ClinVar as [Benign]. Clinvar id is 780328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.18 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00783 (1193/152322) while in subpopulation AFR AF= 0.0262 (1090/41572). AF 95% confidence interval is 0.0249. There are 17 homozygotes in gnomad4. There are 583 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNX2	NM_014801.4 linkuse as main transcript	c.6180A>T	p.Ser2060=	synonymous_variant	33/34	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14 linkuse as main transcript	c.6180A>T	p.Ser2060=	synonymous_variant	33/34	5	NM_014801.4	ENSP00000258229	A2	A6NKB5-1
PCNX2	ENST00000344698.6 linkuse as main transcript	c.2136A>T	p.Ser712=	synonymous_variant	10/10	2		ENSP00000340759	P4	A6NKB5-3
PCNX2	ENST00000462233.5 linkuse as main transcript	c.*1519A>T		3_prime_UTR_variant, NMD_transcript_variant	19/20	2		ENSP00000428488

Frequencies

GnomAD3 genomes

AF:

0.00779

AC:

1186

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00219

AC:

402

AN:

183656

Hom.:

AF XY:

0.00161

AC XY:

159

AN XY:

98468

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.00210

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000248

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000431

Gnomad OTH exome

AF:

0.00204

GnomAD4 exome

AF:

0.00100

AC:

1423

AN:

1418012

Hom.:

Cov.:

AF XY:

0.000870

AC XY:

610

AN XY:

701234

show subpopulations

Gnomad4 AFR exome

AF:

0.0276

Gnomad4 AMR exome

AF:

0.00253

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000238

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.00783

AC:

1193

AN:

152322

Hom.:

Cov.:

AF XY:

0.00783

AC XY:

583

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0262

Gnomad4 AMR

AF:

0.00444

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00286

Hom.:

Bravo

AF:

0.00897

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.093

DANN

Benign

0.60

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