rs9969765

chr9-84874870-G-C

Variant summary

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

The ENST00000304053.11(NTRK2):c.*3053G>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 0.355 in 1,056,410 control chromosomes in the GnomAD database, including 67,792 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 0.41 (12837 hom., cov: 32)
  • Exomes 𝑓: 0.35 (54955 hom.)
• Consequence: NTRK2 ENST00000304053.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.1633+7439G>C		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1633+7439G>C		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61555 AN: 151882 Hom.: 12817 Cov.: 32

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.347 AC: 313613 AN: 904410 Hom.: 54955 Cov.: 31 AF XY: 0.346 AC XY: 144501 AN XY: 417690

Gnomad4 AFR exome AF: 0.502

Gnomad4 AMR exome AF: 0.417

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.516

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.371

GnomAD4 genome AF: 0.405 AC: 61617 AN: 152000 Hom.: 12837 Cov.: 32 AF XY: 0.408 AC XY: 30289 AN XY: 74322

Gnomad4 AFR AF: 0.501

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.403

Alfa AF: 0.376 Hom.: 1372

Bravo AF: 0.415

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.46
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: rs9969765; hg19: chr9-87489785;