rs7020204

chr9-84811272-C-T

Variant summary

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

The ENST00000359847.4(NTRK2):c.*693C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 1,064,048 control chromosomes in the GnomAD database, including 4,286 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 0.097 (788 hom., cov: 32)
  • Exomes 𝑓: 0.086 (3498 hom.)
• Consequence: NTRK2 ENST00000359847.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.1397-49768C>T		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-49768C>T		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14748 AN: 151622 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0855 AC: 78039 AN: 912308 Hom.: 3498 Cov.: 33 AF XY: 0.0852 AC XY: 35903 AN XY: 421174

Gnomad4 AFR exome AF: 0.0959

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0997

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0613

Gnomad4 NFE exome AF: 0.0826

Gnomad4 OTH exome AF: 0.0962

GnomAD4 genome AF: 0.0973 AC: 14762 AN: 151740 Hom.: 788 Cov.: 32 AF XY: 0.0998 AC XY: 7399 AN XY: 74114

Gnomad4 AFR AF: 0.0984

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0963

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0767

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0832 Hom.: 141

Bravo AF: 0.101

Asia WGS AF: 0.153 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	6.2
Dann	Benign	0.76

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: rs7020204; hg19: chr9-87426187; COSMIC: COSV99454694;