chr7-157568929-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002847.5(PTPRN2):​c.2875G>C​(p.Asp959His) variant causes a missense change. The variant allele was found at a frequency of 0.00000254 in 1,577,208 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PTPRN2
NM_002847.5 missense

Scores

10
6
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.13
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.928

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PTPRN2NM_002847.5 linkc.2875G>C p.Asp959His missense_variant Exon 21 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.2875G>C p.Asp959His missense_variant Exon 21 of 23 1 NM_002847.5 ENSP00000374069.4 Q92932-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000211
AC:
3
AN:
1424962
Hom.:
0
Cov.:
33
AF XY:
0.00000141
AC XY:
1
AN XY:
710894
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000185
Gnomad4 OTH exome
AF:
0.0000169
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2875G>C (p.D959H) alteration is located in exon 21 (coding exon 21) of the PTPRN2 gene. This alteration results from a G to C substitution at nucleotide position 2875, causing the aspartic acid (D) at amino acid position 959 to be replaced by a histidine (H). 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
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
.;.;.;D;.
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Pathogenic
1.0
D;D;D;D;D
M_CAP
Benign
0.063
D
MetaRNN
Pathogenic
0.93
D;D;D;D;D
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.2
.;.;.;M;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-6.6
D;D;D;D;.
REVEL
Uncertain
0.61
Sift
Pathogenic
0.0
D;D;D;D;.
Sift4G
Pathogenic
0.0
D;D;D;D;.
Polyphen
1.0
D;D;.;D;.
Vest4
0.96
MutPred
0.81
.;.;.;Gain of MoRF binding (P = 0.05);.;
MVP
0.63
MPC
0.85
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.96
gMVP
0.85

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: rs1196200371; hg19: chr7-157361621; COSMIC: COSV105328712; API