rs1659400

Positions:

• chr9-84711079-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.583+288A>G		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.583+288A>G		intron_variant		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

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.567

Alfa AF: 0.579 Hom.: 3170

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs1659400; hg19: chr9-87325994;