rs1122530

chr9-84849437-A-G

Variant summary

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

The NM_006180.6(NTRK2):c.1397-11603A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,166 control chromosomes in the GnomAD database, including 4,208 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 0.21 (4208 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.315

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.1397-11603A>G		intron_variant		ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-11603A>G		intron_variant		1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32217 AN: 152048 Hom.: 4194 Cov.: 32

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.156

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.212 AC: 32269 AN: 152166 Hom.: 4208 Cov.: 32 AF XY: 0.209 AC XY: 15546 AN XY: 74414

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.156

Gnomad4 EAS AF: 0.0633

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.204

Alfa AF: 0.183 Hom.: 510

Bravo AF: 0.228

Asia WGS AF: 0.120 AC: 418 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	1.0
Dann	Benign	0.36

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: rs1122530; hg19: chr9-87464352; COSMIC: COSV99453595;