chr9-84772992-A-G

Variant names:

• chr9-84772992-A-G
• rs7038866
• NM_006180.6:c.1396+20907A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006180.6(NTRK2):​c.1396+20907A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,120 control chromosomes in the GnomAD database, including 34,691 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 0.67 (34691 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.147
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1396+20907A>G		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.1396+20907A>G		intron_variant	Intron 12 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101888 AN: 152000 Hom.: 34688 Cov.: 32

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.670 AC: 101938 AN: 152120 Hom.: 34691 Cov.: 32 AF XY: 0.674 AC XY: 50156 AN XY: 74364

African (AFR) AF: 0.568 AC: 23571 AN: 41476

American (AMR) AF: 0.693 AC: 10589 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2347 AN: 3472

East Asian (EAS) AF: 0.738 AC: 3826 AN: 5184

South Asian (SAS) AF: 0.717 AC: 3449 AN: 4812

European-Finnish (FIN) AF: 0.776 AC: 8227 AN: 10596

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47692 AN: 67982

Other (OTH) AF: 0.670 AC: 1414 AN: 2112

Alfa AF: 0.685 Hom.: 6288

Bravo AF: 0.658

Asia WGS AF: 0.693 AC: 2407 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		-0.15
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: rs7038866; hg19: chr9-87387907;