rs1554774973
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3PP5
The NM_006180.6(NTRK2):c.2159C>T(p.Thr720Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
NTRK2
NM_006180.6 missense
NM_006180.6 missense
Scores
10
6
1
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
NTRK2 (HGNC:8032): (neurotrophic receptor tyrosine kinase 2) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, NTRK2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.754
PP5
?
Variant 9-84955504-C-T is Pathogenic according to our data. Variant chr9-84955504-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 487685.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NTRK2 | NM_006180.6 | c.2159C>T | p.Thr720Ile | missense_variant | 17/19 | ENST00000277120.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NTRK2 | ENST00000277120.8 | c.2159C>T | p.Thr720Ile | missense_variant | 17/19 | 1 | NM_006180.6 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Obesity, hyperphagia, and developmental delay Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 22, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;D;D
Vest4
MutPred
0.63
.;Loss of catalytic residue at T704 (P = 0.0321);.;Loss of catalytic residue at T704 (P = 0.0321);
MVP
MPC
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