rs1565445

Variant names:

• chr9-85002156-G-A
• rs1565445
• NM_006180.6:c.2173-18050G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-85002156-G-A
• chr9-85002156-G-C
• chr9-85002156-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.2173-18050G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 151,958 control chromosomes in the GnomAD database, including 41,224 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 0.73 (41224 hom., cov: 31)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 20 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.2173-18050G>A		intron_variant	Intron 17 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.2173-18050G>A		intron_variant	Intron 17 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.731 AC: 110950 AN: 151840 Hom.: 41186 Cov.: 31

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.742

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

GnomAD4 genome AF: 0.731 AC: 111046 AN: 151958 Hom.: 41224 Cov.: 31 AF XY: 0.721 AC XY: 53539 AN XY: 74246

African (AFR) AF: 0.819 AC: 33963 AN: 41454

American (AMR) AF: 0.746 AC: 11393 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2579 AN: 3466

East Asian (EAS) AF: 0.383 AC: 1972 AN: 5144

South Asian (SAS) AF: 0.702 AC: 3374 AN: 4804

European-Finnish (FIN) AF: 0.592 AC: 6225 AN: 10520

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.721 AC: 49032 AN: 67982

Other (OTH) AF: 0.741 AC: 1566 AN: 2112

Alfa AF: 0.723 Hom.: 59976

Bravo AF: 0.741

Asia WGS AF: 0.629 AC: 2187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.6
DANN	Benign	0.65
PhyloP100		0.13
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: rs1565445; hg19: chr9-87617071;