chr7-158259226-T-C

Position:

• chr7-158259226-T-C

Variant summary

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

The NM_002847.5(PTPRN2):​c.278-53953A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,984 control chromosomes in the GnomAD database, including 12,777 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 0.40 (12777 hom., cov: 33)
• Consequence: PTPRN2 NM_002847.5 intron
• 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRN2	NM_002847.5	c.278-53953A>G		intron_variant		ENST00000389418.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRN2	ENST00000389418.9	c.278-53953A>G		intron_variant		1	NM_002847.5	P2
PTPRN2	ENST00000389413.7	c.278-53953A>G		intron_variant		1
PTPRN2	ENST00000389416.8	c.227-53953A>G		intron_variant		1		A2
PTPRN2	ENST00000409483.5	c.164-53953A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61199 AN: 151866 Hom.: 12760 Cov.: 33

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.403 AC: 61264 AN: 151984 Hom.: 12777 Cov.: 33 AF XY: 0.399 AC XY: 29635 AN XY: 74296

Gnomad4 AFR AF: 0.503

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.397

Alfa AF: 0.387 Hom.: 2412

Bravo AF: 0.402

Asia WGS AF: 0.307 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.0
DANN	Benign	0.51

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: rs12698191; hg19: chr7-158051918;