2-219295015-C-T

Variant summary

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

The NM_002846.4(PTPRN):​c.2635G>A​(p.Gly879Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,609,560 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

PTPRN
NM_002846.4 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94
Variant links:
Genes affected
PTPRN (HGNC:9676): (protein tyrosine phosphatase receptor type N) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP possesses an extracellular region, a single transmembrane region, and a single catalytic domain, and thus represents a receptor-type PTP. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Dec 2010]

Genome browser will be placed here

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/exons MANE Protein UniProt
PTPRNNM_002846.4 linkc.2635G>A p.Gly879Ser missense_variant 19/23 ENST00000295718.7 NP_002837.1 Q16849-1Q96IA0
PTPRNNM_001199763.2 linkc.2548G>A p.Gly850Ser missense_variant 18/22 NP_001186692.1 Q16849-2
PTPRNNM_001199764.2 linkc.2365G>A p.Gly789Ser missense_variant 19/23 NP_001186693.1 Q16849-3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTPRNENST00000295718.7 linkc.2635G>A p.Gly879Ser missense_variant 19/231 NM_002846.4 ENSP00000295718.2 Q16849-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152210
Hom.:
0
Cov.:
32
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:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000789
AC:
19
AN:
240758
Hom.:
0
AF XY:
0.0000612
AC XY:
8
AN XY:
130680
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000574
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000342
GnomAD4 exome
AF:
0.0000220
AC:
32
AN:
1457234
Hom.:
0
Cov.:
31
AF XY:
0.0000248
AC XY:
18
AN XY:
724624
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:
0.000340
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000499
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152326
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74492
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:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
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 GeneticsSep 24, 2024The c.2635G>A (p.G879S) alteration is located in exon 19 (coding exon 19) of the PTPRN gene. This alteration results from a G to A substitution at nucleotide position 2635, causing the glycine (G) at amino acid position 879 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
0.18
BayesDel_addAF
Benign
-0.072
T
BayesDel_noAF
Uncertain
0.010
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.76
.;D;.
Eigen
Pathogenic
0.71
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Benign
0.55
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
.;L;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-4.6
D;D;.
REVEL
Uncertain
0.40
Sift
Benign
0.064
T;D;.
Sift4G
Uncertain
0.015
D;D;D
Polyphen
0.96
.;D;.
Vest4
0.67
MutPred
0.70
.;Gain of disorder (P = 0.0593);.;
MVP
0.52
MPC
1.3
ClinPred
0.50
D
GERP RS
5.2
Varity_R
0.78
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs548633041; hg19: chr2-220159737; COSMIC: COSV55347735; COSMIC: COSV55347735; API