rs11140800

Positions:

• chr9-84893222-C-A

Variant summary

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

The ENST00000277120.8(NTRK2):​c.1633+25791C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 151,972 control chromosomes in the GnomAD database, including 18,354 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 0.46 (18354 hom., cov: 31)
• Consequence: NTRK2 ENST00000277120.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1633+25791C>A		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1633+25791C>A		intron_variant		1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69746 AN: 151854 Hom.: 18357 Cov.: 31

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.459 AC: 69754 AN: 151972 Hom.: 18354 Cov.: 31 AF XY: 0.458 AC XY: 34041 AN XY: 74270

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.480

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.483

Alfa AF: 0.505 Hom.: 3739

Bravo AF: 0.439

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.68

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: rs11140800; hg19: chr9-87508137; COSMIC: COSV99452078;