rs1659400

Variant names:

• chr9-84711079-A-G
• rs1659400
• NM_006180.6:c.583+288A>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.583+288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,120 control chromosomes in the GnomAD database, including 27,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (27296 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.312
• Publications: 6 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=-0.9).
• BP6: Variant 9-84711079-A-G is Benign according to our data. Variant chr9-84711079-A-G is described in ClinVar as Benign. ClinVar VariationId is 1267695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.583+288A>G		intron_variant	Intron 6 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.583+288A>G		intron_variant	Intron 6 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90636 AN: 152002 Hom.: 27277 Cov.: 32

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.566

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

GnomAD4 genome AF: 0.596 AC: 90703 AN: 152120 Hom.: 27296 Cov.: 32 AF XY: 0.599 AC XY: 44576 AN XY: 74364

African (AFR) AF: 0.652 AC: 27039 AN: 41500

American (AMR) AF: 0.632 AC: 9662 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3472

East Asian (EAS) AF: 0.711 AC: 3684 AN: 5178

South Asian (SAS) AF: 0.591 AC: 2849 AN: 4818

European-Finnish (FIN) AF: 0.606 AC: 6414 AN: 10578

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37453 AN: 67972

Other (OTH) AF: 0.567 AC: 1197 AN: 2110

Alfa AF: 0.581 Hom.: 3335

Bravo AF: 0.600

Asia WGS AF: 0.606 AC: 2108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.31
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: rs1659400; hg19: chr9-87325994;