chr2-219295036-A-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_002846.4(PTPRN):c.2614T>C(p.Phe872Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000471 in 1,612,760 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F872Y) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
PTPRN
NM_002846.4 missense
NM_002846.4 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 4.33
Publications
0 publications found
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 was made for transcript
Our verdict: Uncertain_significance. The variant received 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 |
|---|---|---|---|---|---|---|---|---|
| PTPRN | NM_002846.4 | c.2614T>C | p.Phe872Leu | missense_variant | Exon 19 of 23 | ENST00000295718.7 | NP_002837.1 | |
| PTPRN | NM_001199763.2 | c.2527T>C | p.Phe843Leu | missense_variant | Exon 18 of 22 | NP_001186692.1 | ||
| PTPRN | NM_001199764.2 | c.2344T>C | p.Phe782Leu | missense_variant | Exon 19 of 23 | NP_001186693.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
2
AN:
152132
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000121 AC: 3AN: 248230 AF XY: 0.0000149 show subpopulations
GnomAD2 exomes
AF:
AC:
3
AN:
248230
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000507 AC: 74AN: 1460628Hom.: 0 Cov.: 31 AF XY: 0.0000468 AC XY: 34AN XY: 726584 show subpopulations
GnomAD4 exome
AF:
AC:
74
AN:
1460628
Hom.:
Cov.:
31
AF XY:
AC XY:
34
AN XY:
726584
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33406
American (AMR)
AF:
AC:
0
AN:
44606
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26070
East Asian (EAS)
AF:
AC:
0
AN:
39654
South Asian (SAS)
AF:
AC:
0
AN:
86038
European-Finnish (FIN)
AF:
AC:
0
AN:
53340
Middle Eastern (MID)
AF:
AC:
0
AN:
5758
European-Non Finnish (NFE)
AF:
AC:
72
AN:
1111448
Other (OTH)
AF:
AC:
2
AN:
60308
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.471
Heterozygous variant carriers
0
4
8
13
17
21
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000131 AC: 2AN: 152132Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74340 show subpopulations
GnomAD4 genome
AF:
AC:
2
AN:
152132
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74340
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41456
American (AMR)
AF:
AC:
0
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5174
South Asian (SAS)
AF:
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
AC:
0
AN:
10606
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
1
AN:
67998
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.625
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
2
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Apr 07, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.2614T>C (p.F872L) alteration is located in exon 19 (coding exon 19) of the PTPRN gene. This alteration results from a T to C substitution at nucleotide position 2614, causing the phenylalanine (F) at amino acid position 872 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
0.24
.;B;.
Vest4
MutPred
0.87
.;Loss of sheet (P = 0.1501);.;
MVP
MPC
0.63
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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