Variant rs2289658 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 NM_006180.6(NTRK2):c.1765-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0495 in 1,613,678 control chromosomes in the GnomAD database, including 2,691 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 299 hom., cov: 32)

Exomes 𝑓: 0.049 ( 2392 hom. )

Consequence

NTRK2
NM_006180.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0001185

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.818

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=-0.87).

BP6

Variant 9-84948455-T-C is Benign according to our data. Variant chr9-84948455-T-C is described in ClinVar as [Benign]. Clinvar id is 1279330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 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.1765-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, 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.1765-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_006180.6	ENSP00000277120	P3	Q16620-4

Frequencies

GnomAD3 genomes

AF:

0.0531

AC:

8076

AN:

152066

Hom.:

297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0483

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.0641

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0428

Gnomad OTH

AF:

0.0556

GnomAD3 exomes

AF:

0.0652

AC:

16342

AN:

250804

Hom.:

906

AF XY:

0.0605

AC XY:

8199

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.0488

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.124

Gnomad SAS exome

AF:

0.0549

Gnomad FIN exome

AF:

0.0174

Gnomad NFE exome

AF:

0.0421

Gnomad OTH exome

AF:

0.0575

GnomAD4 exome

AF:

0.0491

AC:

71787

AN:

1461494

Hom.:

2392

Cov.:

AF XY:

0.0485

AC XY:

35256

AN XY:

727052

show subpopulations

Gnomad4 AFR exome

AF:

0.0450

Gnomad4 AMR exome

AF:

0.166

Gnomad4 ASJ exome

AF:

0.0217

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.0517

Gnomad4 FIN exome

AF:

0.0165

Gnomad4 NFE exome

AF:

0.0439

Gnomad4 OTH exome

AF:

0.0527

GnomAD4 genome

AF:

0.0531

AC:

8083

AN:

152184

Hom.:

299

Cov.:

AF XY:

0.0534

AC XY:

3977

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0483

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.127

Gnomad4 SAS

AF:

0.0635

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.0429

Gnomad4 OTH

AF:

0.0569

Alfa

AF:

0.0464

Hom.:

374

Bravo

AF:

0.0616

Asia WGS

AF:

0.118

AC:

411

AN:

3478

EpiCase

AF:

0.0439

EpiControl

AF:

0.0412

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 04, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.66

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00012

dbscSNV1_RF

Benign

0.022

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