18-12814349-T-C
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_002828.4(PTPN2):c.712A>G(p.Lys238Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000133 in 1,431,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PTPN2
NM_002828.4 missense
NM_002828.4 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 5.86
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.15196022).
BS2
?
High AC in GnomAdExome at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTPN2 | NM_002828.4 | c.712A>G | p.Lys238Glu | missense_variant | 7/9 | ENST00000309660.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTPN2 | ENST00000309660.10 | c.712A>G | p.Lys238Glu | missense_variant | 7/9 | 1 | NM_002828.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000627 AC: 14AN: 223424Hom.: 0 AF XY: 0.0000494 AC XY: 6AN XY: 121442
GnomAD3 exomes
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GnomAD4 exome AF: 0.0000133 AC: 19AN: 1431836Hom.: 0 Cov.: 30 AF XY: 0.0000113 AC XY: 8AN XY: 710596
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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ExAC
?
AF:
AC:
7
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 | Dec 03, 2021 | The c.712A>G (p.K238E) 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 712, causing the lysine (K) at amino acid position 238 to be replaced by a glutamic acid (E). 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
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;.;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;L;L;.;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D;.;.;.
REVEL
Uncertain
Sift
Benign
D;.;T;D;.;.;.
Sift4G
Uncertain
T;T;T;T;D;.;.
Polyphen
B;.;.;B;.;.;.
Vest4
MutPred
Loss of ubiquitination at K238 (P = 0.0218);.;Loss of ubiquitination at K238 (P = 0.0218);Loss of ubiquitination at K238 (P = 0.0218);.;.;.;
MVP
MPC
0.30
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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