2-219295015-C-T
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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
NM_002846.4 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 4.94
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]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTPRN | NM_002846.4 | c.2635G>A | p.Gly879Ser | missense_variant | 19/23 | ENST00000295718.7 | NP_002837.1 | |
PTPRN | NM_001199763.2 | c.2548G>A | p.Gly850Ser | missense_variant | 18/22 | NP_001186692.1 | ||
PTPRN | NM_001199764.2 | c.2365G>A | p.Gly789Ser | missense_variant | 19/23 | NP_001186693.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000789 AC: 19AN: 240758Hom.: 0 AF XY: 0.0000612 AC XY: 8AN XY: 130680
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GnomAD4 exome AF: 0.0000220 AC: 32AN: 1457234Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 724624
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GnomAD4 genome AF: 0.00000656 AC: 1AN: 152326Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74492
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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 | Sep 24, 2024 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.
REVEL
Uncertain
Sift
Benign
T;D;.
Sift4G
Uncertain
D;D;D
Polyphen
0.96
.;D;.
Vest4
MutPred
0.70
.;Gain of disorder (P = 0.0593);.;
MVP
MPC
1.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at