chr7-157717791-G-C

Variant names:

• chr7-157717791-G-C
• rs6459806
• NM_002847.5:c.1789-34854C>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.1789-34854C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,180 control chromosomes in the GnomAD database, including 14,922 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 0.44 (14922 hom., cov: 35)
• Consequence: PTPRN2 NM_002847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 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.1789-34854C>G		intron	N/A	NP_002838.2
	PTPRN2	NM_001308268.2		c.1858-34854C>G		intron	N/A	NP_001295197.1
	PTPRN2	NM_130842.4		c.1738-34854C>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.1789-34854C>G		intron	N/A	ENSP00000374069.4
	PTPRN2	ENST00000389416.8	TSL:1	c.1738-34854C>G		intron	N/A	ENSP00000374067.4
	PTPRN2	ENST00000389413.7	TSL:1	c.1702-34854C>G		intron	N/A	ENSP00000374064.3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66392 AN: 152062 Hom.: 14913 Cov.: 35

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.436 AC: 66423 AN: 152180 Hom.: 14922 Cov.: 35 AF XY: 0.435 AC XY: 32336 AN XY: 74386

African (AFR) AF: 0.518 AC: 21514 AN: 41510

American (AMR) AF: 0.410 AC: 6268 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1802 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1964 AN: 5176

South Asian (SAS) AF: 0.414 AC: 1996 AN: 4826

European-Finnish (FIN) AF: 0.358 AC: 3795 AN: 10598

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27778 AN: 67988

Other (OTH) AF: 0.449 AC: 950 AN: 2114

Alfa AF: 0.420 Hom.: 1723

Bravo AF: 0.444

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.6
DANN	Benign	0.60
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6459806; hg19: chr7-157510483;