9-84823244-A-G

Position:

• chr9-84823244-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.1397-37796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,112 control chromosomes in the GnomAD database, including 9,740 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 (9740 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589

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=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1397-37796A>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.1397-37796A>G		intron_variant		1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52728 AN: 151994 Hom.: 9725 Cov.: 33

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.347 AC: 52774 AN: 152112 Hom.: 9740 Cov.: 33 AF XY: 0.345 AC XY: 25635 AN XY: 74380

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.368

Alfa AF: 0.309 Hom.: 958

Bravo AF: 0.359

Asia WGS AF: 0.384 AC: 1332 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.0
DANN	Benign	0.58

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: rs1036914; hg19: chr9-87438159; COSMIC: COSV99453556;