chr11-48144715-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002843.4(PTPRJ):c.2616G>C(p.Glu872Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,613,142 control chromosomes in the GnomAD database, including 244,274 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 18045 hom., cov: 32)

Exomes 𝑓: 0.55 ( 226229 hom. )

Consequence

PTPRJ
NM_002843.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.98

Publications

44 publications found

Variant links:

Genes affected

PTPRJ (HGNC:9673): (protein tyrosine phosphatase receptor type J) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes, including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region containing five fibronectin type III repeats, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. This protein is present in all hematopoietic lineages, and was shown to negatively regulate T cell receptor signaling possibly through interfering with the phosphorylation of Phospholipase C Gamma 1 and Linker for Activation of T Cells. This protein can also dephosphorylate the PDGF beta receptor, and may be involved in UV-induced signal transduction. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PTPRJ Gene-Disease associations (from GenCC):

hereditary nonpolyposis colon cancer
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
thrombocytopenia 10
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, ClinGen
colorectal cancer
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PTPRJ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0584347E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002843.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	NM_002843.4	MANE Select	c.2616G>C	p.Glu872Asp	missense	Exon 13 of 25	NP_002834.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRJ	ENST00000418331.7	TSL:1 MANE Select	c.2616G>C	p.Glu872Asp	missense	Exon 13 of 25	ENSP00000400010.2	Q12913-1
	PTPRJ	ENST00000698881.1		c.2958G>C	p.Glu986Asp	missense	Exon 13 of 25	ENSP00000514003.1	A0A8V8TP51

Frequencies

GnomAD3 genomes

AF:

0.444

AC:

67510

AN:

151934

Hom.:

18035

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.563

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.608

Gnomad MID

AF:

0.475

Gnomad NFE

AF:

0.574

Gnomad OTH

AF:

0.468

GnomAD2 exomes

AF:

0.525

AC:

131735

AN:

250806

AF XY:

0.523

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.649

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.413

Gnomad FIN exome

AF:

0.607

Gnomad NFE exome

AF:

0.576

Gnomad OTH exome

AF:

0.555

GnomAD4 exome

AF:

0.549

AC:

802106

AN:

1461090

Hom.:

226229

Cov.:

AF XY:

0.546

AC XY:

396997

AN XY:

726876

show subpopulations

African (AFR)

AF:

0.118

AC:

3938

AN:

33476

American (AMR)

AF:

0.638

AC:

28553

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.553

AC:

14452

AN:

26134

East Asian (EAS)

AF:

0.460

AC:

18252

AN:

39690

South Asian (SAS)

AF:

0.407

AC:

35065

AN:

86248

European-Finnish (FIN)

AF:

0.606

AC:

32350

AN:

53412

Middle Eastern (MID)

AF:

0.504

AC:

2908

AN:

5768

European-Non Finnish (NFE)

AF:

0.572

AC:

635397

AN:

1111268

Other (OTH)

AF:

0.517

AC:

31191

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

18714

37428

56141

74855

93569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17408

34816

52224

69632

87040

<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:

0.444

AC:

67531

AN:

152052

Hom.:

18045

Cov.:

AF XY:

0.446

AC XY:

33156

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.135

AC:

5617

AN:

41480

American (AMR)

AF:

0.562

AC:

8597

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1912

AN:

3470

East Asian (EAS)

AF:

0.416

AC:

2146

AN:

5160

South Asian (SAS)

AF:

0.419

AC:

2013

AN:

4810

European-Finnish (FIN)

AF:

0.608

AC:

6422

AN:

10562

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.574

AC:

39004

AN:

67972

Other (OTH)

AF:

0.472

AC:

996

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1646

3292

4938

6584

8230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.514

Hom.:

6016

Bravo

AF:

0.432

TwinsUK

AF:

0.567

AC:

2101

ALSPAC

AF:

0.578

AC:

2229

ESP6500AA

AF:

0.149

AC:

654

ESP6500EA

AF:

0.576

AC:

4952

ExAC

AF:

0.515

AC:

62488

EpiCase

AF:

0.567

EpiControl

AF:

0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0090

(source)

DANN

Benign

0.27

DEOGEN2

Benign

0.051

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0000011

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.55

PhyloP100

-4.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.31

REVEL

Benign

0.019

Sift

Benign

0.65

Sift4G

Benign

0.53

Polyphen

0.0070

Vest4

0.032

MutPred

0.21

Gain of sheet (P = 0.0827)

MPC

0.21

ClinPred

0.020

GERP RS

-11

Varity_R

0.031

gMVP

0.23

Mutation Taster

=98/2

polymorphism (auto)

(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

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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