18-12814242-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002828.4(PTPN2):c.819A>G(p.Ile273Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,452,760 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
PTPN2
NM_002828.4 missense
NM_002828.4 missense
Scores
13
5
Clinical Significance
Conservation
PhyloP100: 1.90
Genes affected
PTPN2 (HGNC:9650): (protein tyrosine phosphatase non-receptor type 2) The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. Members of the PTP family share a highly conserved catalytic motif, which is essential for the catalytic activity. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. Epidermal growth factor receptor and the adaptor protein Shc were reported to be substrates of this PTP, which suggested the roles in growth factor mediated cell signaling. Multiple alternatively spliced transcript variants encoding different isoforms have been found. Two highly related but distinctly processed pseudogenes that localize to chromosomes 1 and 13, respectively, have been reported. [provided by RefSeq, May 2011]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN2 | NM_002828.4 | c.819A>G | p.Ile273Met | missense_variant | 7/9 | ENST00000309660.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN2 | ENST00000309660.10 | c.819A>G | p.Ile273Met | missense_variant | 7/9 | 1 | NM_002828.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 6.88e-7 AC: 1AN: 1452760Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1AN XY: 722922
GnomAD4 exome
AF:
AC:
1
AN:
1452760
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
722922
Gnomad4 AFR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
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 submitter | clinical testing | Ambry Genetics | Jul 20, 2022 | The c.819A>G (p.I273M) alteration is located in exon 7 (coding exon 7) of the PTPN2 gene. This alteration results from a A to G substitution at nucleotide position 819, causing the isoleucine (I) at amino acid position 273 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Benign
M;.;M;M;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;N;N;.;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;.;.;.
Sift4G
Uncertain
D;D;D;D;D;.;.
Polyphen
P;.;.;P;.;.;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0728);.;Gain of MoRF binding (P = 0.0728);Gain of MoRF binding (P = 0.0728);.;.;.;
MVP
MPC
0.11
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