7-157621372-G-GGCCAGTTTCCACCGCCCGTAACCCAGGCTTCCTGCCCCCGGGGCTGGTACGTACAGGTCAGCACA

Position:

• chr7-157621372-G-GGCCAGTTTCCACCGCCCGTAACCCAGGCTTCCTGCCCCCGGGGCTGGTACGTACAGGTCAGCACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002847.5(PTPRN2):​c.2333_2334insTGTGCTGACCTGTACGTACCAGCCCCGGGGGCAGGAAGCCTGGGTTACGGGCGGTGGAAACTGGC​(p.Tyr782fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 145,058 control chromosomes in the GnomAD database, including 324 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.022 (324 hom., cov: 34)
  • Exomes 𝑓: 0.018 (1231 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTPRN2 NM_002847.5 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.69

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 -10 ACMG points.

• BP6: Variant 7-157621372-G-GGCCAGTTTCCACCGCCCGTAACCCAGGCTTCCTGCCCCCGGGGCTGGTACGTACAGGTCAGCACA is Benign according to our data. Variant chr7-157621372-G-GGCCAGTTTCCACCGCCCGTAACCCAGGCTTCCTGCCCCCGGGGCTGGTACGTACAGGTCAGCACA is described in ClinVar as [Benign]. Clinvar id is 789293.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0219 (3182/145058) while in subpopulation NFE AF= 0.0303 (1941/64138). AF 95% confidence interval is 0.0291. There are 324 homozygotes in gnomad4. There are 1520 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 324 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PTPRN2	NM_002847.5	c.2333_2334insTGTGCTGACCTGTACGTACCAGCCCCGGGGGCAGGAAGCCTGGGTTACGGGCGGTGGAAACTGGC	p.Tyr782fs	frameshift_variant	15/23	ENST00000389418.9	NP_002838.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PTPRN2	ENST00000389418.9	c.2333_2334insTGTGCTGACCTGTACGTACCAGCCCCGGGGGCAGGAAGCCTGGGTTACGGGCGGTGGAAACTGGC	p.Tyr782fs	frameshift_variant	15/23	1	NM_002847.5	ENSP00000374069.4

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3182 AN: 144936 Hom.: 324 Cov.: 34

Gnomad AFR AF: 0.00940

Gnomad AMI AF: 0.0101

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0439

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0256

Gnomad MID AF: 0.00671

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0253

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0184 AC: 25816 AN: 1402188 Hom.: 1231 Cov.: 36 AF XY: 0.0189 AC XY: 13201 AN XY: 698560

Gnomad4 AFR exome AF: 0.00880

Gnomad4 AMR exome AF: 0.0170

Gnomad4 ASJ exome AF: 0.0520

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0128

Gnomad4 FIN exome AF: 0.0373

Gnomad4 NFE exome AF: 0.0177

Gnomad4 OTH exome AF: 0.0267

GnomAD4 genome AF: 0.0219 AC: 3182 AN: 145058 Hom.: 324 Cov.: 34 AF XY: 0.0214 AC XY: 1520 AN XY: 70984

Gnomad4 AFR AF: 0.00937

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0439

Gnomad4 EAS AF: 0.000389

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0256

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.0250

Alfa AF: 0.0188 Hom.: 13

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1563273056; hg19: chr7-157414064;