rs1187272

Positions:

• chr9-84789171-G-A
• chr9-84789171-G-C
• chr9-84789171-G-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+37086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,950 control chromosomes in the GnomAD database, including 27,280 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 0.58 (27280 hom., cov: 31)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.412

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1396+37086G>A		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1396+37086G>A		intron_variant		1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88297 AN: 151832 Hom.: 27300 Cov.: 31

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.581 AC: 88285 AN: 151950 Hom.: 27280 Cov.: 31 AF XY: 0.586 AC XY: 43535 AN XY: 74250

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.613

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.596

Alfa AF: 0.510 Hom.: 1615

Bravo AF: 0.559

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.64

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: rs1187272; hg19: chr9-87404086; COSMIC: COSV99451938;