rs2277193

chr9-84959094-T-C

Variant summary

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

The NM_006180.6(NTRK2):c.2172+3577T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 152,124 control chromosomes in the GnomAD database, including 10,558 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 0.36 (10558 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.2172+3577T>C		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.2172+3577T>C		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54933 AN: 152006 Hom.: 10542 Cov.: 32

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.362 AC: 54993 AN: 152124 Hom.: 10558 Cov.: 32 AF XY: 0.358 AC XY: 26600 AN XY: 74384

Gnomad4 AFR AF: 0.493

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.333

Alfa AF: 0.320 Hom.: 11906

Bravo AF: 0.379

Asia WGS AF: 0.267 AC: 928 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.015
Dann	Benign	0.38

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: rs2277193; hg19: chr9-87574009;