rs4242630

chr9-84996630-C-T

Variant summary

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

The NM_006180.6(NTRK2):c.2173-23576C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,158 control chromosomes in the GnomAD database, including 40,991 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 (40991 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.866

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.2173-23576C>T		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.2173-23576C>T		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110705 AN: 152040 Hom.: 40954 Cov.: 33

Gnomad AFR AF: 0.816

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.719

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.728 AC: 110800 AN: 152158 Hom.: 40991 Cov.: 33 AF XY: 0.718 AC XY: 53427 AN XY: 74378

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.381

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.719

Gnomad4 OTH AF: 0.739

Alfa AF: 0.726 Hom.: 4985

Bravo AF: 0.739

Asia WGS AF: 0.629 AC: 2187 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.32
Dann	Benign	0.27

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: rs4242630; hg19: chr9-87611545;