Variant 7-157540717-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000389418.9(PTPRN2):c.3045G>T(p.Gln1015His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00955 in 1,561,220 control chromosomes in the GnomAD database, including 93 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 7 hom., cov: 33)

Exomes 𝑓: 0.0099 ( 86 hom. )

Consequence

PTPRN2
ENST00000389418.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.61

Variant links:

Genes affected

PTPRN2 (HGNC:9677): (protein tyrosine phosphatase receptor type N2) This gene encodes a protein with sequence similarity to receptor-like protein tyrosine phosphatases. However, tyrosine phosphatase activity has not been experimentally validated for this protein. Studies of the rat ortholog suggest that the encoded protein may instead function as a phosphatidylinositol phosphatase with the ability to dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 4,5-diphosphate, and this function may be involved in the regulation of insulin secretion. This protein has been identified as an autoantigen in insulin-dependent diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

PTPRN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.479122).

BP6

Variant 7-157540717-C-A is Benign according to our data. Variant chr7-157540717-C-A is described in ClinVar as [Benign]. Clinvar id is 774459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRN2	NM_002847.5 linkuse as main transcript	c.3045G>T	p.Gln1015His	missense_variant	23/23	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9 linkuse as main transcript	c.3045G>T	p.Gln1015His	missense_variant	23/23	1	NM_002847.5	ENSP00000374069	P2	Q92932-1

Frequencies

GnomAD3 genomes

AF:

0.00643

AC:

979

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00604

AC:

1041

AN:

172386

Hom.:

AF XY:

0.00657

AC XY:

601

AN XY:

91526

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00408

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.00261

Gnomad NFE exome

AF:

0.0101

Gnomad OTH exome

AF:

0.00699

GnomAD4 exome

AF:

0.00989

AC:

13935

AN:

1408894

Hom.:

Cov.:

AF XY:

0.00977

AC XY:

6801

AN XY:

696236

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.00402

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0000818

Gnomad4 SAS exome

AF:

0.00197

Gnomad4 FIN exome

AF:

0.00243

Gnomad4 NFE exome

AF:

0.0118

Gnomad4 OTH exome

AF:

0.00758

GnomAD4 genome

AF:

0.00643

AC:

979

AN:

152326

Hom.:

Cov.:

AF XY:

0.00587

AC XY:

437

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00216

Gnomad4 AMR

AF:

0.00470

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00962

Hom.:

Bravo

AF:

0.00645

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.0117

AC:

100

ExAC

AF:

0.00333

AC:

392

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	PTPRN2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.94

MutationTaster

Benign

1.0

D;D;D;D;D

ClinPred

0.032

GERP RS

3.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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