Variant chr9-84670792-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The ENST00000277120.8(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
ENST00000277120.8 missense

Scores

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]

NTRK2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), NTRK2. . Trascript score misZ 5.2832 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 58, undetermined early-onset epileptic encephalopathy, West syndrome, obesity, hyperphagia, and developmental delay.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6 linkuse as main transcript	c.44T>A	p.Leu15His	missense_variant	2/19	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8 linkuse as main transcript	c.44T>A	p.Leu15His	missense_variant	2/19	1	NM_006180.6	ENSP00000277120	P3	Q16620-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251274

Hom.:

AF XY:

0.00

AC XY:

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.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 31, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.48

.;T;.;.;.;.;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.80

T;T;T;T;T;.;.;.

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.60

D;D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

0.90

L;L;L;L;L;L;L;L

MutationTaster

Benign

0.77

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.58

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over