7-157578083-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002847.5(PTPRN2):​c.2554G>A​(p.Gly852Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000552 in 1,613,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

PTPRN2
NM_002847.5 missense

Scores

2
10
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.67
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36258304).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTPRN2NM_002847.5 linkc.2554G>A p.Gly852Ser missense_variant 18/23 ENST00000389418.9 NP_002838.2 Q92932-1I6L9F8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTPRN2ENST00000389418.9 linkc.2554G>A p.Gly852Ser missense_variant 18/231 NM_002847.5 ENSP00000374069.4 Q92932-1

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
250972
Hom.:
0
AF XY:
0.0000295
AC XY:
4
AN XY:
135684
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000383
AC:
56
AN:
1461298
Hom.:
0
Cov.:
33
AF XY:
0.0000303
AC XY:
22
AN XY:
726952
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000360
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.000217
AC:
33
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.000269
AC XY:
20
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.000481
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000580
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000149
Hom.:
0
Bravo
AF:
0.000242
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000577
AC:
7
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJun 11, 2024The c.2554G>A (p.G852S) alteration is located in exon 18 (coding exon 18) of the PTPRN2 gene. This alteration results from a G to A substitution at nucleotide position 2554, causing the glycine (G) at amino acid position 852 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.090
T
BayesDel_noAF
Uncertain
0.010
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.53
.;.;.;D;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.92
D;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.36
T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.7
.;.;.;L;.
PrimateAI
Uncertain
0.52
T
PROVEAN
Pathogenic
-5.7
D;D;D;D;.
REVEL
Uncertain
0.32
Sift
Uncertain
0.0030
D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;.
Polyphen
0.99
D;D;.;D;.
Vest4
0.81
MVP
0.72
MPC
0.77
ClinPred
0.55
D
GERP RS
5.3
Varity_R
0.85
gMVP
0.68

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

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

Other links and lift over

dbSNP: rs373071385; hg19: chr7-157370775; COSMIC: COSV66104631; COSMIC: COSV66104631; API