Variant 9-84671000-C-T 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.212+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,590,222 control chromosomes in the GnomAD database, including 461,132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40402 hom., cov: 32)

Exomes 𝑓: 0.76 ( 420730 hom. )

Consequence

NTRK2
NM_006180.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.830

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:

NTRK2 (HGNC:):

NTRK2 links:

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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 9-84671000-C-T is Benign according to our data. Variant chr9-84671000-C-T is described in ClinVar as [Benign]. Clinvar id is 1276690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.765 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.212+40C>T		intron_variant		ENST00000277120.8	NP_006171.2	Q16620-4A0A024R230Q5VWE5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8 linkuse as main transcript	c.212+40C>T		intron_variant		1	NM_006180.6	ENSP00000277120.3		Q16620-4

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110163

AN:

151942

Hom.:

40374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.611

Gnomad AMI

AF:

0.762

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.769

Gnomad EAS

AF:

0.757

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.802

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.753

GnomAD3 exomes

AF:

0.758

AC:

174012

AN:

229630

Hom.:

65915

AF XY:

0.761

AC XY:

94987

AN XY:

124842

show subpopulations

Gnomad AFR exome

AF:

0.612

Gnomad AMR exome

AF:

0.784

Gnomad ASJ exome

AF:

0.772

Gnomad EAS exome

AF:

0.772

Gnomad SAS exome

AF:

0.728

Gnomad FIN exome

AF:

0.796

Gnomad NFE exome

AF:

0.771

Gnomad OTH exome

AF:

0.764

GnomAD4 exome

AF:

0.764

AC:

1098708

AN:

1438162

Hom.:

420730

Cov.:

AF XY:

0.764

AC XY:

546606

AN XY:

715698

show subpopulations

Gnomad4 AFR exome

AF:

0.609

Gnomad4 AMR exome

AF:

0.779

Gnomad4 ASJ exome

AF:

0.775

Gnomad4 EAS exome

AF:

0.737

Gnomad4 SAS exome

AF:

0.731

Gnomad4 FIN exome

AF:

0.791

Gnomad4 NFE exome

AF:

0.771

Gnomad4 OTH exome

AF:

0.761

GnomAD4 genome

AF:

0.725

AC:

110241

AN:

152060

Hom.:

40402

Cov.:

AF XY:

0.727

AC XY:

54014

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.611

Gnomad4 AMR

AF:

0.745

Gnomad4 ASJ

AF:

0.769

Gnomad4 EAS

AF:

0.757

Gnomad4 SAS

AF:

0.736

Gnomad4 FIN

AF:

0.802

Gnomad4 NFE

AF:

0.771

Gnomad4 OTH

AF:

0.750

Alfa

AF:

0.744

Hom.:

8839

Bravo

AF:

0.716

Asia WGS

AF:

0.716

AC:

2490

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Obesity, hyperphagia, and developmental delay

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Developmental and epileptic encephalopathy, 58

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

1.5

DANN

Benign

0.46

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