2-219297035-G-A

Position:

chr2-219297035-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002846.4(PTPRN):c.2186C>T(p.Ala729Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PTPRN
NM_002846.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.28

Variant links:

Genes affected

PTPRN (HGNC:9676): (protein tyrosine phosphatase receptor type N) 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, a single transmembrane region, and a single catalytic domain, and thus represents a receptor-type PTP. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Dec 2010]

PTPRN links:

PTPRN (HGNC:):

PTPRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRN	NM_002846.4 linkuse as main transcript	c.2186C>T	p.Ala729Val	missense_variant	15/23	ENST00000295718.7	NP_002837.1	Q16849-1Q96IA0
PTPRN	NM_001199763.2 linkuse as main transcript	c.2099C>T	p.Ala700Val	missense_variant	14/22		NP_001186692.1	Q16849-2
PTPRN	NM_001199764.2 linkuse as main transcript	c.1916C>T	p.Ala639Val	missense_variant	15/23		NP_001186693.1	Q16849-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PTPRN	ENST00000295718.7 linkuse as main transcript	c.2186C>T	p.Ala729Val	missense_variant	15/23	1	NM_002846.4	ENSP00000295718.2	Q16849-1
PTPRN	ENST00000409251.7 linkuse as main transcript	c.2099C>T	p.Ala700Val	missense_variant	14/22	1		ENSP00000386638.3	Q16849-2
PTPRN	ENST00000423636.6 linkuse as main transcript	c.1916C>T	p.Ala639Val	missense_variant	15/23	2		ENSP00000392598.2	Q16849-3
PTPRN	ENST00000462351.5 linkuse as main transcript	n.2660C>T		non_coding_transcript_exon_variant	13/20	2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251314

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461746

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727184

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:

0.0000188

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000151

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

Aug 20, 2023

The c.2186C>T (p.A729V) alteration is located in exon 15 (coding exon 15) of the PTPRN gene. This alteration results from a C to T substitution at nucleotide position 2186, causing the alanine (A) at amino acid position 729 to be replaced by a valine (V). 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

Pathogenic

0.76

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.77

.;D;.

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.048

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-0.41

MutationAssessor

Uncertain

2.9

.;M;.

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.6

D;D;.

REVEL

Uncertain

0.46

Sift

Uncertain

0.0020

D;D;.

Sift4G

Uncertain

0.0070

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.77

MutPred

0.55

.;Loss of disorder (P = 0.0706);.;

MVP

0.61

MPC

1.3

ClinPred

0.98

GERP RS

4.2

Varity_R

0.77

gMVP

0.76

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

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