rs10868229

Positions:

• chr9-84848647-A-G

Variant summary

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

The NM_006180.6(NTRK2):​c.1397-12393A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 152,132 control chromosomes in the GnomAD database, including 11,683 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 0.35 (11683 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1397-12393A>G		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-12393A>G		intron_variant		1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53472 AN: 152014 Hom.: 11677 Cov.: 32

Gnomad AFR AF: 0.0874

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.371

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

GnomAD4 genome AF: 0.352 AC: 53476 AN: 152132 Hom.: 11683 Cov.: 32 AF XY: 0.352 AC XY: 26179 AN XY: 74352

Gnomad4 AFR AF: 0.0871

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.508

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.368

Alfa AF: 0.411 Hom.: 1792

Bravo AF: 0.331

Asia WGS AF: 0.331 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.010
DANN	Benign	0.20

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: rs10868229; hg19: chr9-87463562; COSMIC: COSV99452027;