NM_002847.5:c.164-27362T>A

Variant names:

• chr7-158344294-A-T
• rs4909189
• NM_002847.5:c.164-27362T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-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 rank	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.164-27362T>A		intron_variant	Intron 2 of 22	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.164-27362T>A		intron_variant	Intron 2 of 22	1	NM_002847.5	ENSP00000374069.4
PTPRN2	ENST00000389416.8	c.113-27362T>A		intron_variant	Intron 1 of 21	1		ENSP00000374067.4
PTPRN2	ENST00000389413.7	c.164-27362T>A		intron_variant	Intron 2 of 21	1		ENSP00000374064.3
PTPRN2	ENST00000409483.5	c.164-139021T>A		intron_variant	Intron 2 of 21	2		ENSP00000387114.1

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

African (AFR) AF: 0.462 AC: 19123 AN: 41434

American (AMR) AF: 0.214 AC: 3273 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1065 AN: 5160

South Asian (SAS) AF: 0.149 AC: 720 AN: 4822

European-Finnish (FIN) AF: 0.241 AC: 2553 AN: 10592

Middle Eastern (MID) AF: 0.336 AC: 98 AN: 292

European-Non Finnish (NFE) AF: 0.258 AC: 17517 AN: 67956

Other (OTH) AF: 0.301 AC: 633 AN: 2106

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
PhyloP100		-0.75
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: rs4909189; hg19: chr7-158136986;