Genetic Variant PTPRN2:c.113-43026G>A (chr7-158532811-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002847.5(PTPRN2):c.113-43026G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 534,420 control chromosomes in the GnomAD database, including 9,953 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2262 hom., cov: 32)

Exomes 𝑓: 0.18 ( 7691 hom. )

Consequence

PTPRN2
NM_002847.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390

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:

MIR595 (HGNC:32851): (microRNA 595) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR595 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN2	NM_002847.5 link	c.113-43026G>A		intron_variant	Intron 1 of 22	ENST00000389418.9	NP_002838.2	Q92932-1I6L9F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9 link	c.113-43026G>A		intron_variant	Intron 1 of 22	1	NM_002847.5	ENSP00000374069.4		Q92932-1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23240

AN:

151956

Hom.:

2266

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.113

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.158

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.192

AC:

48117

AN:

250982

Hom.:

5587

AF XY:

0.184

AC XY:

24983

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0606

Gnomad AMR exome

AF:

0.332

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.250

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.303

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.198

GnomAD4 exome

AF:

0.184

AC:

70182

AN:

382346

Hom.:

7691

Cov.:

AF XY:

0.175

AC XY:

38182

AN XY:

217660

show subpopulations

Gnomad4 AFR exome

AF:

0.0634

Gnomad4 AMR exome

AF:

0.334

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.302

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.178

GnomAD4 genome

AF:

0.153

AC:

23235

AN:

152074

Hom.:

2262

Cov.:

AF XY:

0.159

AC XY:

11848

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0625

Gnomad4 AMR

AF:

0.235

Gnomad4 ASJ

AF:

0.149

Gnomad4 EAS

AF:

0.254

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.310

Gnomad4 NFE

AF:

0.158

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.148

Hom.:

1003

Bravo

AF:

0.148

Asia WGS

AF:

0.220

AC:

767

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.5

DANN

Benign

0.77

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over