chr7-158344294-A-T

Position:

• chr7-158344294-A-T

Variant summary

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

The NM_002847.5(PTPRN2):​c.164-27362T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 152,008 control chromosomes in the GnomAD database, including 8,040 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 0.31 (8040 hom., cov: 31)
• Consequence: PTPRN2 NM_002847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTPRN2	NM_002847.5	c.164-27362T>A		intron_variant		ENST00000389418.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTPRN2	ENST00000389418.9	c.164-27362T>A		intron_variant		1	NM_002847.5	P2
PTPRN2	ENST00000389413.7	c.164-27362T>A		intron_variant		1
PTPRN2	ENST00000389416.8	c.113-27362T>A		intron_variant		1		A2
PTPRN2	ENST00000409483.5	c.164-139021T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46424 AN: 151892 Hom.: 8032 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.306 AC: 46463 AN: 152008 Hom.: 8040 Cov.: 31 AF XY: 0.302 AC XY: 22414 AN XY: 74298

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.301

Alfa AF: 0.282 Hom.: 859

Bravo AF: 0.314

Asia WGS AF: 0.166 AC: 579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.26

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: rs4909189; hg19: chr7-158136986;