rs1187362

Positions:

• chr9-84723352-T-A
• chr9-84723352-T-C
• chr9-84723352-T-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.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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.584-221T>A		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.584-221T>A		intron_variant		1	NM_006180.6	P3

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

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.685

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.715

Gnomad4 FIN AF: 0.759

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.658

Alfa AF: 0.600 Hom.: 1819

Bravo AF: 0.652

Asia WGS AF: 0.673 AC: 2339 AN: 3476

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	-0.80
CADD	Benign	10
DANN	Benign	0.66

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: rs1187362; hg19: chr9-87338267;