9-84777667-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.1396+25582C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,910 control chromosomes in the GnomAD database, including 29,617 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 0.62 (29617 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.833

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• 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	UniProt
NTRK2	NM_006180.6	c.1396+25582C>T		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1396+25582C>T		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93827 AN: 151792 Hom.: 29629 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.626

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

GnomAD4 genome AF: 0.618 AC: 93840 AN: 151910 Hom.: 29617 Cov.: 32 AF XY: 0.621 AC XY: 46129 AN XY: 74252

Gnomad4 AFR AF: 0.496

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.727

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.618

Alfa AF: 0.652 Hom.: 30967

Bravo AF: 0.602

Asia WGS AF: 0.628 AC: 2183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.63
Dann	Benign	0.62

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: rs10465180; hg19: chr9-87392582; COSMIC: COSV99451925;