9-84670792-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006180.6(NTRK2):​c.44T>A​(p.Leu15His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

NTRK2
NM_006180.6 missense

Scores

11
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53
Variant links:
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
NTRK2NM_006180.6 linkc.44T>A p.Leu15His missense_variant Exon 2 of 19 ENST00000277120.8 NP_006171.2 Q16620-4A0A024R230Q5VWE5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTRK2ENST00000277120.8 linkc.44T>A p.Leu15His missense_variant Exon 2 of 19 1 NM_006180.6 ENSP00000277120.3 Q16620-4

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251274
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Aug 31, 2021
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Uncertain
0.074
D
BayesDel_noAF
Benign
-0.13
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.48
.;T;.;.;.;.;T;.
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Benign
0.72
D
LIST_S2
Benign
0.80
T;T;T;T;T;.;.;.
M_CAP
Uncertain
0.18
D
MetaRNN
Uncertain
0.60
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.17
T
MutationAssessor
Benign
0.90
L;L;L;L;L;L;L;L
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-2.0
N;N;D;D;D;N;N;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.013
D;D;D;D;D;D;D;D
Sift4G
Benign
0.080
T;T;D;D;D;T;T;D
Polyphen
0.48
P;D;P;P;P;P;D;P
Vest4
0.68
MutPred
0.35
Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);Loss of stability (P = 0.0332);
MVP
0.72
MPC
1.6
ClinPred
0.61
D
GERP RS
5.0
Varity_R
0.29
gMVP
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs756957794; hg19: chr9-87285707; API