dbSNP rs77573141: PTPN2:p.Val234Ile (chr18-12817161-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002828.4(PTPN2):c.700G>A(p.Val234Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,612,216 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 13 hom. )

Consequence

PTPN2
NM_002828.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.961

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008156508).

BP6

Variant 18-12817161-C-T is Benign according to our data. Variant chr18-12817161-C-T is described in ClinVar as Benign. ClinVar VariationId is 711701.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 = 0.00775 (1179/152078) while in subpopulation AFR AF = 0.027 (1122/41492). AF 95% confidence interval is 0.0257. There are 8 homozygotes in GnomAd4. There are 543 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1179 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002828.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN2	NM_002828.4	MANE Select	c.700G>A	p.Val234Ile	missense	Exon 6 of 9	NP_002819.2	P17706-1
PTPN2	NM_001207013.2		c.769G>A	p.Val257Ile	missense	Exon 7 of 11	NP_001193942.1	P17706-4
PTPN2	NM_080422.3		c.700G>A	p.Val234Ile	missense	Exon 6 of 10	NP_536347.1	P17706-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PTPN2	ENST00000309660.10	TSL:1 MANE Select	c.700G>A	p.Val234Ile	missense	Exon 6 of 9	ENSP00000311857.3	P17706-1
PTPN2	ENST00000591115.5	TSL:1	c.769G>A	p.Val257Ile	missense	Exon 7 of 11	ENSP00000466936.1	P17706-4
PTPN2	ENST00000327283.7	TSL:1	c.700G>A	p.Val234Ile	missense	Exon 6 of 10	ENSP00000320298.3	P17706-2

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1177

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00315

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.00198

AC:

494

AN:

249742

AF XY:

0.00145

show subpopulations

Gnomad AFR exome

AF:

0.0278

Gnomad AMR exome

AF:

0.000907

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000619

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000769

AC:

1123

AN:

1460138

Hom.:

Cov.:

AF XY:

0.000676

AC XY:

491

AN XY:

726318

show subpopulations

African (AFR)

AF:

0.0274

AC:

913

AN:

33370

American (AMR)

AF:

0.00131

AC:

AN:

44270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000816

AC:

AN:

85816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00174

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000450

AC:

AN:

1111476

Other (OTH)

AF:

0.00141

AC:

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00775

AC:

1179

AN:

152078

Hom.:

Cov.:

AF XY:

0.00730

AC XY:

543

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.0270

AC:

1122

AN:

41492

American (AMR)

AF:

0.00314

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67982

Other (OTH)

AF:

0.00285

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

121

182

242

303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.00873

ESP6500AA

AF:

0.0259

AC:

114

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00270

AC:

328

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.16

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0082

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.97

PhyloP100

0.96

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.46

REVEL

Benign

0.13

Sift

Benign

0.11

Sift4G

Benign

0.068

Polyphen

0.0010

Vest4

0.084

MVP

0.36

MPC

0.073

ClinPred

0.0063

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.035

gMVP

0.30

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over