rs1867283

Variant names:

• chr9-84835851-G-A
• rs1867283
• NM_006180.6:c.1397-25189G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84835851-G-A
• chr9-84835851-G-C
• chr9-84835851-G-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.1397-25189G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,060 control chromosomes in the GnomAD database, including 13,959 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 0.40 (13959 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 22 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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1397-25189G>A		intron_variant	Intron 12 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-25189G>A		intron_variant	Intron 12 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60846 AN: 151942 Hom.: 13956 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.430

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

GnomAD4 genome AF: 0.400 AC: 60862 AN: 152060 Hom.: 13959 Cov.: 32 AF XY: 0.401 AC XY: 29841 AN XY: 74324

African (AFR) AF: 0.158 AC: 6547 AN: 41478

American (AMR) AF: 0.482 AC: 7361 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1958 AN: 3466

East Asian (EAS) AF: 0.467 AC: 2412 AN: 5162

South Asian (SAS) AF: 0.533 AC: 2567 AN: 4816

European-Finnish (FIN) AF: 0.461 AC: 4867 AN: 10564

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

European-Non Finnish (NFE) AF: 0.495 AC: 33624 AN: 67984

Other (OTH) AF: 0.428 AC: 904 AN: 2114

Alfa AF: 0.463 Hom.: 34533

Bravo AF: 0.390

Asia WGS AF: 0.442 AC: 1541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.29
DANN	Benign	0.80
PhyloP100		-1.6
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: rs1867283; hg19: chr9-87450766; COSMIC: COSV52858184;