rs7048278

Positions:

• chr9-84745238-G-A
• chr9-84745238-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006180.6(NTRK2):​c.1296+165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,892 control chromosomes in the GnomAD database, including 28,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.60 (28114 hom., cov: 30)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.178

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-84745238-G-A is Benign according to our data. Variant chr9-84745238-G-A is described in ClinVar as [Benign]. Clinvar id is 1266519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1296+165G>A		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1296+165G>A		intron_variant		1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90620 AN: 151774 Hom.: 28133 Cov.: 30

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.597 AC: 90606 AN: 151892 Hom.: 28114 Cov.: 30 AF XY: 0.601 AC XY: 44594 AN XY: 74204

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.622

Gnomad4 ASJ AF: 0.662

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.606

Alfa AF: 0.619 Hom.: 4351

Bravo AF: 0.578

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.57

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: rs7048278; hg19: chr9-87360153; COSMIC: COSV99451875;