rs1211166

chr9-84671077-G-Achr9-84671077-G-Cchr9-84671077-G-T

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.212+117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 959,496 control chromosomes in the GnomAD database, including 303,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.77 (45543 hom., cov: 34)
  • Exomes 𝑓: 0.80 (257665 hom.)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.912

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=-0.88).
• BP6: Variant 9-84671077-G-A is Benign according to our data. Variant chr9-84671077-G-A is described in ClinVar as [Benign]. Clinvar id is 1178699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.212+117G>A		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.212+117G>A		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117320 AN: 152074 Hom.: 45509 Cov.: 34

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.798 AC: 643829 AN: 807304 Hom.: 257665 AF XY: 0.795 AC XY: 334777 AN XY: 420844

Gnomad4 AFR exome AF: 0.688

Gnomad4 AMR exome AF: 0.819

Gnomad4 ASJ exome AF: 0.795

Gnomad4 EAS exome AF: 0.766

Gnomad4 SAS exome AF: 0.746

Gnomad4 FIN exome AF: 0.824

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.795

GnomAD4 genome AF: 0.771 AC: 117409 AN: 152192 Hom.: 45543 Cov.: 34 AF XY: 0.773 AC XY: 57520 AN XY: 74394

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.804

Gnomad4 OTH AF: 0.786

Alfa AF: 0.784 Hom.: 6014

Bravo AF: 0.766

Asia WGS AF: 0.739 AC: 2572 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.7
Dann	Benign	0.44

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: rs1211166; hg19: chr9-87285992;