rs2013566

chr9-84811383-A-Gchr9-84811383-A-T

Variant summary

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

The ENST00000359847.4(NTRK2):c.*804A>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 0.105 in 1,065,824 control chromosomes in the GnomAD database, including 8,419 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 0.17 (3441 hom., cov: 32)
  • Exomes 𝑓: 0.093 (4978 hom.)
• Consequence: NTRK2 ENST00000359847.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286

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 = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.1397-49657A>G		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-49657A>G		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26360 AN: 152070 Hom.: 3432 Cov.: 32

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.0975

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0766

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.151

GnomAD4 exome AF: 0.0934 AC: 85295 AN: 913636 Hom.: 4978 Cov.: 33 AF XY: 0.0925 AC XY: 39001 AN XY: 421726

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.102

Gnomad4 FIN exome AF: 0.0654

Gnomad4 NFE exome AF: 0.0837

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.174 AC: 26412 AN: 152188 Hom.: 3441 Cov.: 32 AF XY: 0.173 AC XY: 12909 AN XY: 74418

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0975

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0766

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.156

Alfa AF: 0.0967 Hom.: 1244

Bravo AF: 0.189

Asia WGS AF: 0.176 AC: 611 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	1.1
Dann	Benign	0.55

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: rs2013566; hg19: chr9-87426298; COSMIC: COSV99454697;