rs1122307

chr7-157540682-G-Achr7-157540682-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002847.5(PTPRN2):c.*32C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0809 in 1,484,268 control chromosomes in the GnomAD database, including 5,156 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 0.076 (475 hom., cov: 33)
  • Exomes 𝑓: 0.081 (4681 hom.)
• Consequence: PTPRN2 NM_002847.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRN2	NM_002847.5	c.*32C>T		3_prime_UTR_variant	23/23	ENST00000389418.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRN2	ENST00000389418.9	c.*32C>T		3_prime_UTR_variant	23/23	1	NM_002847.5	P2

Frequencies

GnomAD3 genomes AF: 0.0761 AC: 11573 AN: 152122 Hom.: 475 Cov.: 33

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.0860

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0781

Gnomad OTH AF: 0.0617

GnomAD3 exomes AF: 0.0874 AC: 13466 AN: 154076 Hom.: 676 AF XY: 0.0864 AC XY: 7041 AN XY: 81496

Gnomad AFR exome AF: 0.0562

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.0415

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.0820

Gnomad FIN exome AF: 0.0789

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.0827

GnomAD4 exome AF: 0.0815 AC: 108554 AN: 1332028 Hom.: 4681 Cov.: 28 AF XY: 0.0819 AC XY: 54054 AN XY: 660366

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.0429

Gnomad4 EAS exome AF: 0.139

Gnomad4 SAS exome AF: 0.0821

Gnomad4 FIN exome AF: 0.0747

Gnomad4 NFE exome AF: 0.0808

Gnomad4 OTH exome AF: 0.0806

GnomAD4 genome AF: 0.0761 AC: 11579 AN: 152240 Hom.: 475 Cov.: 33 AF XY: 0.0776 AC XY: 5777 AN XY: 74412

Gnomad4 AFR AF: 0.0558

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.0850

Gnomad4 FIN AF: 0.0792

Gnomad4 NFE AF: 0.0782

Gnomad4 OTH AF: 0.0639

Alfa AF: 0.0567 Hom.: 92

Bravo AF: 0.0771

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.31
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs1122307; hg19: chr7-157333376; COSMIC: COSV67021437;