9-84678542-T-C

Variant names:

• chr9-84678542-T-C
• rs1187352
• NM_006180.6:c.212+7582T>C

Variant summary

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

The NM_006180.6(NTRK2):​c.212+7582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,108 control chromosomes in the GnomAD database, including 37,607 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 0.70 (37607 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.86
• Publications: 13 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	NM_006180.6	MANE Select	c.212+7582T>C		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.212+7582T>C		intron	N/A	NP_001018074.1
	NTRK2	NM_001369532.1		c.212+7582T>C		intron	N/A	NP_001356461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.212+7582T>C		intron	N/A	ENSP00000277120.3
	NTRK2	ENST00000323115.11	TSL:1	c.212+7582T>C		intron	N/A	ENSP00000314586.5
	NTRK2	ENST00000304053.11	TSL:1	c.212+7582T>C		intron	N/A	ENSP00000306167.7

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106552 AN: 151990 Hom.: 37567 Cov.: 33

Gnomad AFR AF: 0.736

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.662

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.701 AC: 106654 AN: 152108 Hom.: 37607 Cov.: 33 AF XY: 0.704 AC XY: 52329 AN XY: 74328

African (AFR) AF: 0.736 AC: 30532 AN: 41496

American (AMR) AF: 0.756 AC: 11560 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2257 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4303 AN: 5168

South Asian (SAS) AF: 0.707 AC: 3411 AN: 4824

European-Finnish (FIN) AF: 0.690 AC: 7291 AN: 10560

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.662 AC: 45022 AN: 67984

Other (OTH) AF: 0.699 AC: 1476 AN: 2112

Alfa AF: 0.691 Hom.: 14036

Bravo AF: 0.707

Asia WGS AF: 0.725 AC: 2521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0030
DANN	Benign	0.36
PhyloP100		-3.9
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: rs1187352; hg19: chr9-87293457;