9-84794396-C-T

Variant names:

• chr9-84794396-C-T
• rs1443444
• NM_006180.6:c.1396+42311C>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.1396+42311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,008 control chromosomes in the GnomAD database, including 23,274 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 (23274 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• 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: 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006180.6. 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
	NTRK2	NM_006180.6	MANE Select	c.1396+42311C>T		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.1396+42311C>T		intron	N/A	NP_001018074.1	Q548C2
	NTRK2	NM_001369532.1		c.1396+42311C>T		intron	N/A	NP_001356461.1	Q16620-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.1396+42311C>T		intron	N/A	ENSP00000277120.3	Q16620-4
	NTRK2	ENST00000323115.11	TSL:1	c.1360+42311C>T		intron	N/A	ENSP00000314586.5	A0A8J8YUT9
	NTRK2	ENST00000304053.11	TSL:1	c.1396+42311C>T		intron	N/A	ENSP00000306167.7	Q16620-3

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77212 AN: 151890 Hom.: 23286 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.508 AC: 77203 AN: 152008 Hom.: 23274 Cov.: 32 AF XY: 0.514 AC XY: 38213 AN XY: 74288

African (AFR) AF: 0.164 AC: 6789 AN: 41450

American (AMR) AF: 0.584 AC: 8913 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.649 AC: 2251 AN: 3466

East Asian (EAS) AF: 0.672 AC: 3470 AN: 5162

South Asian (SAS) AF: 0.633 AC: 3048 AN: 4816

European-Finnish (FIN) AF: 0.707 AC: 7455 AN: 10550

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43462 AN: 67980

Other (OTH) AF: 0.543 AC: 1145 AN: 2110

Alfa AF: 0.443 Hom.: 1514

Bravo AF: 0.482

Asia WGS AF: 0.577 AC: 2005 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.39
PhyloP100		-1.4
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: rs1443444; hg19: chr9-87409311;