rs1565445

chr9-85002156-G-A

Variant summary

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

The NM_006180.6(NTRK2):c.2173-18050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,958 control chromosomes in the GnomAD database, including 41,224 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 0.73 (41224 hom., cov: 31)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.2173-18050G>A		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.2173-18050G>A		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.731 AC: 110950 AN: 151840 Hom.: 41186 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.742

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.731 AC: 111046 AN: 151958 Hom.: 41224 Cov.: 31 AF XY: 0.721 AC XY: 53539 AN XY: 74246

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.741

Alfa AF: 0.733 Hom.: 7100

Bravo AF: 0.741

Asia WGS AF: 0.629 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.6
Dann	Benign	0.65

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: rs1565445; hg19: chr9-87617071;