rs11140793

Positions:

• chr9-84876565-A-C
• chr9-84876565-A-G

Variant summary

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

The NM_001018065.2(NTRK2):​c.*4748A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,056,196 control chromosomes in the GnomAD database, including 15,590 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 0.18 (2718 hom., cov: 32)
  • Exomes 𝑓: 0.17 (12872 hom.)
• Consequence: NTRK2 NM_001018065.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1633+9134A>C		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1633+9134A>C		intron_variant		1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27787 AN: 152100 Hom.: 2715 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.167 AC: 150628 AN: 903978 Hom.: 12872 Cov.: 31 AF XY: 0.166 AC XY: 69444 AN XY: 417496

Gnomad4 AFR exome AF: 0.248

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.183 AC: 27813 AN: 152218 Hom.: 2718 Cov.: 32 AF XY: 0.180 AC XY: 13436 AN XY: 74452

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0503

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.183

Alfa AF: 0.131 Hom.: 494

Bravo AF: 0.189

Asia WGS AF: 0.104 AC: 361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.73
DANN	Benign	0.53

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: rs11140793; hg19: chr9-87491480; COSMIC: COSV99452062;