Variant rs2289656 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000277120.8(NTRK2):c.1937+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,612,644 control chromosomes in the GnomAD database, including 24,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1953 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22225 hom. )

Consequence

NTRK2
ENST00000277120.8 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.26

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-84948647-G-A is Benign according to our data. Variant chr9-84948647-G-A is described in ClinVar as [Benign]. Clinvar id is 1249612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6 linkuse as main transcript	c.1937+13G>A		intron_variant		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.1937+13G>A		intron_variant		1	NM_006180.6	ENSP00000277120	P3	Q16620-4

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23329

AN:

152072

Hom.:

1956

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.0351

Gnomad SAS

AF:

0.0913

Gnomad FIN

AF:

0.171

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.164

GnomAD3 exomes

AF:

0.150

AC:

37451

AN:

249854

Hom.:

3174

AF XY:

0.151

AC XY:

20363

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.246

Gnomad EAS exome

AF:

0.0332

Gnomad SAS exome

AF:

0.100

Gnomad FIN exome

AF:

0.166

Gnomad NFE exome

AF:

0.183

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.170

AC:

247774

AN:

1460454

Hom.:

22225

Cov.:

AF XY:

0.169

AC XY:

122517

AN XY:

726502

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.127

Gnomad4 ASJ exome

AF:

0.242

Gnomad4 EAS exome

AF:

0.0378

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.162

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.165

GnomAD4 genome

AF:

0.153

AC:

23328

AN:

152190

Hom.:

1953

Cov.:

AF XY:

0.151

AC XY:

11241

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.248

Gnomad4 EAS

AF:

0.0354

Gnomad4 SAS

AF:

0.0916

Gnomad4 FIN

AF:

0.171

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.182

Hom.:

2864

Bravo

AF:

0.150

Asia WGS

AF:

0.0910

AC:

319

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Developmental and epileptic encephalopathy, 58

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Obesity, hyperphagia, and developmental delay

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.096

DANN

Benign

0.59

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