rs1619120

chr9-84687281-A-Gchr9-84687281-A-T

Variant summary

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

The NM_006180.6(NTRK2):c.213-14878A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 152,058 control chromosomes in the GnomAD database, including 27,734 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 0.60 (27734 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21

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 (AMR) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.213-14878A>G		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.213-14878A>G		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91531 AN: 151940 Hom.: 27707 Cov.: 32

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.619

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.603 AC: 91615 AN: 152058 Hom.: 27734 Cov.: 32 AF XY: 0.606 AC XY: 45006 AN XY: 74302

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.643

Gnomad4 SAS AF: 0.605

Gnomad4 FIN AF: 0.636

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.597

Alfa AF: 0.600 Hom.: 42658

Bravo AF: 0.602

Asia WGS AF: 0.585 AC: 2039 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	1.4
Dann	Benign	0.31

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: rs1619120; hg19: chr9-87302196;