9-84703613-G-C

Position:

• chr9-84703613-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006180.6(NTRK2):​c.359+1194G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,138 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.045 (208 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.359+1194G>C		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.359+1194G>C		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6797 AN: 152020 Hom.: 208 Cov.: 33

Gnomad AFR AF: 0.0730

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0159

Gnomad EAS AF: 0.00385

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.0326

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0338

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0447 AC: 6799 AN: 152138 Hom.: 208 Cov.: 33 AF XY: 0.0444 AC XY: 3301 AN XY: 74392

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.0530

Gnomad4 ASJ AF: 0.0159

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0326

Gnomad4 NFE AF: 0.0338

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0445 Hom.: 17

Bravo AF: 0.0490

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.7
DANN	Benign	0.65

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: rs7041260; hg19: chr9-87318528;