rs11788168

Variant names:

• chr9-84885514-T-A
• rs11788168
• NM_006180.6:c.1633+18083T>A

Variant summary

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

The NM_006180.6(NTRK2):​c.1633+18083T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 149,338 control chromosomes in the GnomAD database, including 1,518 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 0.12 (1518 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 2 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 = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1633+18083T>A		intron_variant	Intron 14 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1633+18083T>A		intron_variant	Intron 14 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17517 AN: 149222 Hom.: 1513 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0133

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0719

Gnomad EAS AF: 0.0508

Gnomad SAS AF: 0.0715

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0673

Gnomad NFE AF: 0.0650

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.118 AC: 17550 AN: 149338 Hom.: 1518 Cov.: 32 AF XY: 0.116 AC XY: 8432 AN XY: 72976

African (AFR) AF: 0.242 AC: 10004 AN: 41272

American (AMR) AF: 0.128 AC: 1827 AN: 14228

Ashkenazi Jewish (ASJ) AF: 0.0719 AC: 248 AN: 3450

East Asian (EAS) AF: 0.0511 AC: 258 AN: 5044

South Asian (SAS) AF: 0.0716 AC: 340 AN: 4750

European-Finnish (FIN) AF: 0.0253 AC: 262 AN: 10344

Middle Eastern (MID) AF: 0.0655 AC: 19 AN: 290

European-Non Finnish (NFE) AF: 0.0650 AC: 4360 AN: 67074

Other (OTH) AF: 0.107 AC: 221 AN: 2060

Alfa AF: 0.0870 Hom.: 119

Bravo AF: 0.127

Asia WGS AF: 0.0710 AC: 248 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.78
PhyloP100		0.31
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: rs11788168; hg19: chr9-87500429;