rs768757935

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002847.5(PTPRN2):​c.2539C>G​(p.Pro847Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P847T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

PTPRN2
NM_002847.5 missense

Scores

2
4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.55
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPRN2NM_002847.5 linkc.2539C>G p.Pro847Ala missense_variant Exon 18 of 23 ENST00000389418.9 NP_002838.2 Q92932-1I6L9F8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PTPRN2ENST00000389418.9 linkc.2539C>G p.Pro847Ala missense_variant Exon 18 of 23 1 NM_002847.5 ENSP00000374069.4 Q92932-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.028
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.37
.;.;.;T;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.16
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.87
D;D;D;D;D
M_CAP
Benign
0.015
T
MetaRNN
Uncertain
0.62
D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.56
.;.;.;N;.
PrimateAI
Uncertain
0.61
T
PROVEAN
Pathogenic
-5.9
D;D;D;D;.
REVEL
Benign
0.25
Sift
Benign
0.097
T;T;T;T;.
Sift4G
Benign
0.32
T;T;T;T;.
Polyphen
0.11
B;B;.;B;.
Vest4
0.58
MutPred
0.46
.;.;.;Gain of sheet (P = 0.1539);.;
MVP
0.55
MPC
0.68
ClinPred
0.95
D
GERP RS
4.5
Varity_R
0.44
gMVP
0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-157370790; API