rs11140778

Variant names:

• chr9-84832243-A-T
• rs11140778
• NM_006180.6:c.1397-28797A>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.1397-28797A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,208 control chromosomes in the GnomAD database, including 2,527 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 0.16 (2527 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 6 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

LOC124902193 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1397-28797A>T		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.1397-28797A>T		intron_variant	Intron 12 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24901 AN: 152090 Hom.: 2520 Cov.: 33

Gnomad AFR AF: 0.0460

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.164 AC: 24918 AN: 152208 Hom.: 2527 Cov.: 33 AF XY: 0.164 AC XY: 12231 AN XY: 74410

African (AFR) AF: 0.0460 AC: 1910 AN: 41542

American (AMR) AF: 0.209 AC: 3201 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 720 AN: 3470

East Asian (EAS) AF: 0.171 AC: 884 AN: 5176

South Asian (SAS) AF: 0.174 AC: 841 AN: 4820

European-Finnish (FIN) AF: 0.186 AC: 1970 AN: 10596

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14776 AN: 67998

Other (OTH) AF: 0.167 AC: 354 AN: 2116

Alfa AF: 0.185 Hom.: 351

Bravo AF: 0.157

Asia WGS AF: 0.167 AC: 582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.8
DANN	Benign	0.86
PhyloP100		0.33
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: rs11140778; hg19: chr9-87447158;