rs2489162

Variant names:

• chr9-84718827-G-A
• rs2489162
• NM_006180.6:c.584-4746G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84718827-G-A
• chr9-84718827-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006180.6(NTRK2):​c.584-4746G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,026 control chromosomes in the GnomAD database, including 26,960 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 0.59 (26960 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 3 publications found

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]

NTRK2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 58

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• obesity, hyperphagia, and developmental delay

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006180.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	NM_006180.6	MANE Select	c.584-4746G>A		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.584-4746G>A		intron	N/A	NP_001018074.1	Q548C2
	NTRK2	NM_001369532.1		c.584-4746G>A		intron	N/A	NP_001356461.1	Q16620-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.584-4746G>A		intron	N/A	ENSP00000277120.3	Q16620-4
	NTRK2	ENST00000323115.11	TSL:1	c.584-4746G>A		intron	N/A	ENSP00000314586.5	A0A8J8YUT9
	NTRK2	ENST00000304053.11	TSL:1	c.584-4746G>A		intron	N/A	ENSP00000306167.7	Q16620-3

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90100 AN: 151908 Hom.: 26942 Cov.: 32

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.504

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.587

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.593 AC: 90166 AN: 152026 Hom.: 26960 Cov.: 32 AF XY: 0.597 AC XY: 44333 AN XY: 74318

African (AFR) AF: 0.644 AC: 26689 AN: 41450

American (AMR) AF: 0.631 AC: 9646 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3470

East Asian (EAS) AF: 0.711 AC: 3672 AN: 5164

South Asian (SAS) AF: 0.588 AC: 2837 AN: 4826

European-Finnish (FIN) AF: 0.608 AC: 6419 AN: 10560

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37371 AN: 67956

Other (OTH) AF: 0.565 AC: 1192 AN: 2110

Alfa AF: 0.588 Hom.: 4916

Bravo AF: 0.596

Asia WGS AF: 0.602 AC: 2094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2489162; hg19: chr9-87333742;