rs1619120

Variant names:

• chr9-84687281-A-G
• rs1619120
• NM_006180.6:c.213-14878A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-84687281-A-G
• chr9-84687281-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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: G2P, Labcorp Genetics (formerly Invitae)
• 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	NM_006180.6	MANE Select	c.213-14878A>G		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.213-14878A>G		intron	N/A	NP_001018074.1
	NTRK2	NM_001369532.1		c.213-14878A>G		intron	N/A	NP_001356461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.213-14878A>G		intron	N/A	ENSP00000277120.3
	NTRK2	ENST00000323115.11	TSL:1	c.213-14878A>G		intron	N/A	ENSP00000314586.5
	NTRK2	ENST00000304053.11	TSL:1	c.213-14878A>G		intron	N/A	ENSP00000306167.7

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

African (AFR) AF: 0.561 AC: 23282 AN: 41484

American (AMR) AF: 0.671 AC: 10264 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2063 AN: 3470

East Asian (EAS) AF: 0.643 AC: 3323 AN: 5166

South Asian (SAS) AF: 0.605 AC: 2908 AN: 4808

European-Finnish (FIN) AF: 0.636 AC: 6720 AN: 10560

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41079 AN: 67966

Other (OTH) AF: 0.597 AC: 1260 AN: 2112

Alfa AF: 0.600 Hom.: 71940

Bravo AF: 0.602

Asia WGS AF: 0.585 AC: 2039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.31
PhyloP100		-2.2
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: rs1619120; hg19: chr9-87302196;