rs1078947

Positions:

• chr9-84948337-T-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.1765-125T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 990,600 control chromosomes in the GnomAD database, including 351,382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (50796 hom., cov: 32)
  • Exomes 𝑓: 0.85 (300586 hom.)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31

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=-0.91).
• BP6: Variant 9-84948337-T-C is Benign according to our data. Variant chr9-84948337-T-C is described in ClinVar as [Benign]. Clinvar id is 1235842.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1765-125T>C		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1765-125T>C		intron_variant		1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124013 AN: 152028 Hom.: 50759 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.860

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.856

Gnomad OTH AF: 0.811

GnomAD4 exome AF: 0.845 AC: 708902 AN: 838454 Hom.: 300586 AF XY: 0.846 AC XY: 368468 AN XY: 435460

Gnomad4 AFR exome AF: 0.752

Gnomad4 AMR exome AF: 0.828

Gnomad4 ASJ exome AF: 0.856

Gnomad4 EAS exome AF: 0.712

Gnomad4 SAS exome AF: 0.865

Gnomad4 FIN exome AF: 0.796

Gnomad4 NFE exome AF: 0.859

Gnomad4 OTH exome AF: 0.833

GnomAD4 genome AF: 0.816 AC: 124103 AN: 152146 Hom.: 50796 Cov.: 32 AF XY: 0.813 AC XY: 60471 AN XY: 74370

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.747

Gnomad4 SAS AF: 0.860

Gnomad4 FIN AF: 0.785

Gnomad4 NFE AF: 0.856

Gnomad4 OTH AF: 0.808

Alfa AF: 0.846 Hom.: 52773

Bravo AF: 0.815

Asia WGS AF: 0.785 AC: 2730 AN: 3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.91
CADD	Benign	0.88
DANN	Benign	0.45

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: rs1078947; hg19: chr9-87563252; COSMIC: COSV52878124;