rs3780634

Positions:

• chr9-84873803-A-G

Variant summary

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

The ENST00000304053.11(NTRK2):​c.*1986A>G 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 1,056,366 control chromosomes in the GnomAD database, including 15,515 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 (2697 hom., cov: 32)
  • Exomes 𝑓: 0.17 (12818 hom.)
• Consequence: NTRK2 ENST00000304053.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.33

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1633+6372A>G		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+6372A>G		intron_variant		1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27725 AN: 152056 Hom.: 2695 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0628

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.195

GnomAD4 exome AF: 0.166 AC: 150502 AN: 904192 Hom.: 12818 Cov.: 26 AF XY: 0.166 AC XY: 69396 AN XY: 417644

Gnomad4 AFR exome AF: 0.225

Gnomad4 AMR exome AF: 0.219

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.0652

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.182 AC: 27755 AN: 152174 Hom.: 2697 Cov.: 32 AF XY: 0.181 AC XY: 13477 AN XY: 74404

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0631

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.193

Alfa AF: 0.162 Hom.: 1693

Bravo AF: 0.191

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0020
DANN	Benign	0.42

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: rs3780634; hg19: chr9-87488718; COSMIC: COSV99452056;