7-157621372-G-GGCCAGTTTCCACCGCCCGTAACCCAGGCTTCCTGCCCCCGGGGCTGGTACGTACAGGTCAGCACA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.69
Variant links:
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]

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ACMG classification

Classification made for transcript

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
PTPRN2NM_002847.5 linkc.2333_2334insTGTGCTGACCTGTACGTACCAGCCCCGGGGGCAGGAAGCCTGGGTTACGGGCGGTGGAAACTGGC p.Tyr782fs frameshift_variant 15/23 ENST00000389418.9 NP_002838.2 Q92932-1I6L9F8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTPRN2ENST00000389418.9 linkc.2333_2334insTGTGCTGACCTGTACGTACCAGCCCCGGGGGCAGGAAGCCTGGGTTACGGGCGGTGGAAACTGGC p.Tyr782fs frameshift_variant 15/231 NM_002847.5 ENSP00000374069.4 Q92932-1

Frequencies

GnomAD3 genomes
AF:
0.0220
AC:
3182
AN:
144936
Hom.:
324
Cov.:
34
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1563273056; hg19: chr7-157414064; API