7-157717503-C-T

Position:

• chr7-157717503-C-T

Variant summary

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

The NM_002847.5(PTPRN2):​c.1789-34566G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,200 control chromosomes in the GnomAD database, including 14,932 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 (14932 hom., cov: 35)
• Consequence: PTPRN2 NM_002847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.788

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.1789-34566G>A		intron_variant		ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.1789-34566G>A		intron_variant		1	NM_002847.5	ENSP00000374069.4
PTPRN2	ENST00000389416.8	c.1738-34566G>A		intron_variant		1		ENSP00000374067.4
PTPRN2	ENST00000389413.7	c.1702-34566G>A		intron_variant		1		ENSP00000374064.3
PTPRN2	ENST00000409483.5	c.1675-34566G>A		intron_variant		2		ENSP00000387114.1

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66414 AN: 152082 Hom.: 14923 Cov.: 35

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.437 AC: 66445 AN: 152200 Hom.: 14932 Cov.: 35 AF XY: 0.435 AC XY: 32362 AN XY: 74416

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.449

Alfa AF: 0.406 Hom.: 14689

Bravo AF: 0.444

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.2
DANN	Benign	0.38

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

Other links and lift over

dbSNP: rs6459804; hg19: chr7-157510195;