rs1187362

Variant names:

• chr9-84723352-T-A
• rs1187362
• NM_006180.6:c.584-221T>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84723352-T-A
• chr9-84723352-T-C
• chr9-84723352-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006180.6(NTRK2):​c.584-221T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,098 control chromosomes in the GnomAD database, including 33,983 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33983 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-84723352-T-A is Benign according to our data. Variant chr9-84723352-T-A is described in ClinVar as Benign. ClinVar VariationId is 1230119.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 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.584-221T>A		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.584-221T>A		intron	N/A	NP_001018074.1
	NTRK2	NM_001369532.1		c.584-221T>A		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.584-221T>A		intron	N/A	ENSP00000277120.3
	NTRK2	ENST00000323115.11	TSL:1	c.584-221T>A		intron	N/A	ENSP00000314586.5
	NTRK2	ENST00000304053.11	TSL:1	c.584-221T>A		intron	N/A	ENSP00000306167.7

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100939 AN: 151980 Hom.: 33978 Cov.: 33

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.664 AC: 100983 AN: 152098 Hom.: 33983 Cov.: 33 AF XY: 0.667 AC XY: 49624 AN XY: 74356

African (AFR) AF: 0.559 AC: 23177 AN: 41484

American (AMR) AF: 0.685 AC: 10468 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2390 AN: 3466

East Asian (EAS) AF: 0.732 AC: 3797 AN: 5186

South Asian (SAS) AF: 0.715 AC: 3441 AN: 4812

European-Finnish (FIN) AF: 0.759 AC: 8024 AN: 10570

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47505 AN: 67978

Other (OTH) AF: 0.658 AC: 1389 AN: 2110

Alfa AF: 0.600 Hom.: 1819

Bravo AF: 0.652

Asia WGS AF: 0.673 AC: 2339 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.66
PhyloP100		0.065
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: rs1187362; hg19: chr9-87338267;