rs10746752

Positions:

• chr9-84980801-G-A

Variant summary

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

The NM_006180.6(NTRK2):​c.2172+25284G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,274 control chromosomes in the GnomAD database, including 1,156 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 0.099 (1156 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.2172+25284G>A		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.2172+25284G>A		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15018 AN: 152156 Hom.: 1154 Cov.: 33

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0882

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.0987 AC: 15027 AN: 152274 Hom.: 1156 Cov.: 33 AF XY: 0.102 AC XY: 7602 AN XY: 74460

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.0996

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0882

Gnomad4 OTH AF: 0.0893

Alfa AF: 0.0953 Hom.: 351

Bravo AF: 0.103

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.60
DANN	Benign	0.67

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: rs10746752; hg19: chr9-87595716; COSMIC: COSV52858271;