9-84737873-C-T

Position:

• chr9-84737873-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006180.6(NTRK2):​c.1160-4019C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,100 control chromosomes in the GnomAD database, including 27,800 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (27800 hom., cov: 30)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1160-4019C>T		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1160-4019C>T		intron_variant		1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.587 AC: 88655 AN: 150982 Hom.: 27817 Cov.: 30

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.618

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.676

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.607

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.587 AC: 88646 AN: 151100 Hom.: 27800 Cov.: 30 AF XY: 0.592 AC XY: 43699 AN XY: 73842

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.618

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.600

Alfa AF: 0.646 Hom.: 25382

Bravo AF: 0.565

Asia WGS AF: 0.618 AC: 2150 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs3780632; hg19: chr9-87352788;