rs10274279

Variant names:

• chr7-157594749-T-C
• rs10274279
• NM_002847.5:c.2496+489A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002847.5(PTPRN2):​c.2496+489A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,158 control chromosomes in the GnomAD database, including 2,670 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 0.17 (2670 hom., cov: 33)
• Consequence: PTPRN2 NM_002847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 15 publications found

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]

ENSG00000298556 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002847.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRN2	NM_002847.5	MANE Select	c.2496+489A>G		intron	N/A	NP_002838.2
	PTPRN2	NM_001308268.2		c.2565+489A>G		intron	N/A	NP_001295197.1
	PTPRN2	NM_130842.4		c.2445+489A>G		intron	N/A	NP_570857.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTPRN2	ENST00000389418.9	TSL:1 MANE Select	c.2496+489A>G		intron	N/A	ENSP00000374069.4
	PTPRN2	ENST00000389416.8	TSL:1	c.2445+489A>G		intron	N/A	ENSP00000374067.4
	PTPRN2	ENST00000389413.7	TSL:1	c.2409+489A>G		intron	N/A	ENSP00000374064.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25212 AN: 152040 Hom.: 2665 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25257 AN: 152158 Hom.: 2670 Cov.: 33 AF XY: 0.160 AC XY: 11898 AN XY: 74378

African (AFR) AF: 0.294 AC: 12180 AN: 41468

American (AMR) AF: 0.120 AC: 1835 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3472

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5174

South Asian (SAS) AF: 0.120 AC: 578 AN: 4824

European-Finnish (FIN) AF: 0.0690 AC: 732 AN: 10612

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8632 AN: 67998

Other (OTH) AF: 0.145 AC: 305 AN: 2108

Alfa AF: 0.143 Hom.: 5435

Bravo AF: 0.175

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0050
DANN	Benign	0.14
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10274279; hg19: chr7-157387441;