ENST00000687386.1:c.2125-12752T>C

Variant names:

• chr9-85082239-T-C
• rs615189
• ENST00000687386.1:c.2125-12752T>C

Variant summary

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

The ENST00000687386.1(NTRK2):​c.2125-12752T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 151,950 control chromosomes in the GnomAD database, including 20,312 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 0.51 (20312 hom., cov: 31)
• Consequence: NTRK2 ENST00000687386.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000687386.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000687386.1		c.2125-12752T>C		intron	N/A	ENSP00000508723.1	A0A8I5KVH8

Frequencies

GnomAD3 genomes AF: 0.511 AC: 77591 AN: 151834 Hom.: 20306 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.511 AC: 77636 AN: 151950 Hom.: 20312 Cov.: 31 AF XY: 0.509 AC XY: 37836 AN XY: 74274

African (AFR) AF: 0.619 AC: 25674 AN: 41448

American (AMR) AF: 0.418 AC: 6379 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1703 AN: 3468

East Asian (EAS) AF: 0.342 AC: 1768 AN: 5170

South Asian (SAS) AF: 0.364 AC: 1753 AN: 4810

European-Finnish (FIN) AF: 0.528 AC: 5560 AN: 10538

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33287 AN: 67940

Other (OTH) AF: 0.490 AC: 1031 AN: 2106

Alfa AF: 0.491 Hom.: 66997

Bravo AF: 0.509

Asia WGS AF: 0.371 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.78
PhyloP100		-3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs615189; hg19: chr9-87697154; COSMIC: COSV60370319;