18-12817349-G-T

Position:

chr18-12817349-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002828.4(PTPN2):c.512C>A(p.Thr171Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00257 in 1,613,352 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 50 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 45 hom. )

Consequence

PTPN2
NM_002828.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.82

Variant links:

Genes affected

PTPN2 (HGNC:9650): (protein tyrosine phosphatase non-receptor type 2) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]

PTPN2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007090658).

BP6

Variant 18-12817349-G-T is Benign according to our data. Variant chr18-12817349-G-T is described in ClinVar as [Benign]. Clinvar id is 775462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2142/152230) while in subpopulation AFR AF= 0.0489 (2031/41524). AF 95% confidence interval is 0.0471. There are 50 homozygotes in gnomad4. There are 1020 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPN2	NM_002828.4 link	c.512C>A	p.Thr171Lys	missense_variant	6/9	ENST00000309660.10	NP_002819.2	P17706-1Q59F91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPN2	ENST00000309660.10 link	c.512C>A	p.Thr171Lys	missense_variant	6/9	1	NM_002828.4	ENSP00000311857.3		P17706-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2136

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0489

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00498

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:

0.000162

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00351

AC:

882

AN:

251118

Hom.:

AF XY:

0.00256

AC XY:

347

AN XY:

135760

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00137

AC:

2002

AN:

1461122

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

829

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.0494

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.0141

AC:

2142

AN:

152230

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1020

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0489

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00294

Hom.:

Bravo

AF:

0.0160

ESP6500AA

AF:

0.0504

AC:

222

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00423

AC:

514

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

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	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.16

.;.;.;T;.;.;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.86

D;T;D;D;D;.;D

MetaRNN

Benign

0.0071

T;T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.63

N;.;N;N;.;.;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.41

N;.;N;N;.;.;.

REVEL

Benign

0.24

Sift

Benign

0.22

T;.;T;T;.;.;.

Sift4G

Benign

0.32

T;T;T;T;T;.;.

Polyphen

0.013

B;.;.;B;.;.;.

Vest4

0.25

MVP

0.49

MPC

1.2

ClinPred

0.011

GERP RS

3.1

Varity_R

0.12

gMVP

0.47

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