rs1822420

Positions:

• chr9-84852361-T-C

Variant summary

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

The NM_006180.6(NTRK2):​c.1397-8679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,206 control chromosomes in the GnomAD database, including 57,964 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 0.87 (57964 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1397-8679T>C		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-8679T>C		intron_variant		1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132624 AN: 152088 Hom.: 57926 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.872 AC: 132719 AN: 152206 Hom.: 57964 Cov.: 32 AF XY: 0.871 AC XY: 64819 AN XY: 74394

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.887

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.899

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.864

Gnomad4 OTH AF: 0.859

Alfa AF: 0.867 Hom.: 42526

Bravo AF: 0.876

Asia WGS AF: 0.839 AC: 2919 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.81

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: rs1822420; hg19: chr9-87467276; COSMIC: COSV99452036;