rs1822420

Variant names:

• chr9-84852361-T-C
• rs1822420
• NM_006180.6:c.1397-8679T>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.1397-8679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,206 control chromosomes in the GnomAD database, including 57,964 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 0.87 (57964 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 3 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 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.1397-8679T>C		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.1397-14882T>C		intron	N/A	NP_001018074.1
	NTRK2	NM_001369532.1		c.1397-14882T>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.1397-8679T>C		intron	N/A	ENSP00000277120.3
	NTRK2	ENST00000323115.11	TSL:1	c.1361-14882T>C		intron	N/A	ENSP00000314586.5
	NTRK2	ENST00000304053.11	TSL:1	c.1397-14882T>C		intron	N/A	ENSP00000306167.7

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132624 AN: 152088 Hom.: 57926 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.887

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.864

Gnomad OTH AF: 0.858

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

GnomAD4 genome AF: 0.872 AC: 132719 AN: 152206 Hom.: 57964 Cov.: 32 AF XY: 0.871 AC XY: 64819 AN XY: 74394

African (AFR) AF: 0.903 AC: 37522 AN: 41534

American (AMR) AF: 0.887 AC: 13575 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2893 AN: 3470

East Asian (EAS) AF: 0.733 AC: 3791 AN: 5170

South Asian (SAS) AF: 0.899 AC: 4336 AN: 4822

European-Finnish (FIN) AF: 0.849 AC: 8977 AN: 10576

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.864 AC: 58770 AN: 68018

Other (OTH) AF: 0.859 AC: 1810 AN: 2108

Alfa AF: 0.868 Hom.: 49797

Bravo AF: 0.876

Asia WGS AF: 0.839 AC: 2919 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		0.20
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: rs1822420; hg19: chr9-87467276;