7-158532811-C-T

Variant names:

• chr7-158532811-C-T
• rs4909237
• NM_002847.5:c.113-43026G>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.113-43026G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 534,420 control chromosomes in the GnomAD database, including 9,953 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 0.15 (2262 hom., cov: 32)
  • Exomes 𝑓: 0.18 (7691 hom.)
• Consequence: PTPRN2 NM_002847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 21 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]

MIR595 (HGNC:32851): (microRNA 595) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.113-43026G>A		intron_variant	Intron 1 of 22	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.113-43026G>A		intron_variant	Intron 1 of 22	1	NM_002847.5	ENSP00000374069.4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23240 AN: 151956 Hom.: 2266 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.192 AC: 48117 AN: 250982 AF XY: 0.184

Gnomad AFR exome AF: 0.0606

Gnomad AMR exome AF: 0.332

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.250

Gnomad FIN exome AF: 0.303

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.184 AC: 70182 AN: 382346 Hom.: 7691 Cov.: 0 AF XY: 0.175 AC XY: 38182 AN XY: 217660

African (AFR) AF: 0.0634 AC: 666 AN: 10512

American (AMR) AF: 0.334 AC: 12137 AN: 36294

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 1738 AN: 11744

East Asian (EAS) AF: 0.256 AC: 3368 AN: 13166

South Asian (SAS) AF: 0.136 AC: 9083 AN: 66762

European-Finnish (FIN) AF: 0.302 AC: 9753 AN: 32300

Middle Eastern (MID) AF: 0.152 AC: 433 AN: 2842

European-Non Finnish (NFE) AF: 0.156 AC: 30031 AN: 192004

Other (OTH) AF: 0.178 AC: 2973 AN: 16722

GnomAD4 genome AF: 0.153 AC: 23235 AN: 152074 Hom.: 2262 Cov.: 32 AF XY: 0.159 AC XY: 11848 AN XY: 74308

African (AFR) AF: 0.0625 AC: 2596 AN: 41522

American (AMR) AF: 0.235 AC: 3589 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 516 AN: 3466

East Asian (EAS) AF: 0.254 AC: 1305 AN: 5144

South Asian (SAS) AF: 0.135 AC: 646 AN: 4800

European-Finnish (FIN) AF: 0.310 AC: 3277 AN: 10556

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10762 AN: 67988

Other (OTH) AF: 0.183 AC: 387 AN: 2112

Alfa AF: 0.149 Hom.: 1165

Bravo AF: 0.148

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.77
PhyloP100		-0.039
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: rs4909237; hg19: chr7-158325503; COSMIC: COSV66039150; COSMIC: COSV66039150;