rs2001314

Variant names:

• chr7-158267052-C-G
• rs2001314
• NM_002847.5:c.277+49767G>C

Variant summary

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

The NM_002847.5(PTPRN2):​c.277+49767G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,176 control chromosomes in the GnomAD database, including 4,605 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 0.24 (4605 hom., cov: 33)
• Consequence: PTPRN2 NM_002847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 3 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.277+49767G>C		intron_variant	Intron 3 of 22	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.277+49767G>C		intron_variant	Intron 3 of 22	1	NM_002847.5	ENSP00000374069.4
PTPRN2	ENST00000389416.8	c.226+49767G>C		intron_variant	Intron 2 of 21	1		ENSP00000374067.4
PTPRN2	ENST00000389413.7	c.277+49767G>C		intron_variant	Intron 3 of 21	1		ENSP00000374064.3
PTPRN2	ENST00000409483.5	c.164-61779G>C		intron_variant	Intron 2 of 21	2		ENSP00000387114.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36291 AN: 152056 Hom.: 4602 Cov.: 33

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.267

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

GnomAD4 genome AF: 0.239 AC: 36307 AN: 152176 Hom.: 4605 Cov.: 33 AF XY: 0.235 AC XY: 17514 AN XY: 74392

African (AFR) AF: 0.173 AC: 7169 AN: 41540

American (AMR) AF: 0.207 AC: 3165 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1091 AN: 3470

East Asian (EAS) AF: 0.169 AC: 875 AN: 5164

South Asian (SAS) AF: 0.177 AC: 855 AN: 4822

European-Finnish (FIN) AF: 0.276 AC: 2923 AN: 10592

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19101 AN: 67976

Other (OTH) AF: 0.266 AC: 562 AN: 2110

Alfa AF: 0.256 Hom.: 625

Bravo AF: 0.233

Asia WGS AF: 0.187 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.49
PhyloP100		-0.35
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: rs2001314; hg19: chr7-158059744; COSMIC: COSV67029479;