rs7038236

chr9-84873487-C-Achr9-84873487-C-T

Variant summary

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

The ENST00000304053.11(NTRK2):c.*1670C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,058,988 control chromosomes in the GnomAD database, including 15,489 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 (2671 hom., cov: 32)
  • Exomes 𝑓: 0.17 (12818 hom.)
• Consequence: NTRK2 ENST00000304053.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.1633+6056C>A		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1633+6056C>A		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27561 AN: 151812 Hom.: 2668 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.166 AC: 150696 AN: 907058 Hom.: 12818 Cov.: 33 AF XY: 0.166 AC XY: 69482 AN XY: 418924

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.0375

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.173

GnomAD4 genome AF: 0.182 AC: 27587 AN: 151930 Hom.: 2671 Cov.: 32 AF XY: 0.179 AC XY: 13319 AN XY: 74252

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0495

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.180

Alfa AF: 0.131 Hom.: 375

Bravo AF: 0.187

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.4
Dann	Benign	0.48

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: rs7038236; hg19: chr9-87488402; COSMIC: COSV99452055;