9-84893781-G-T

Position:

• chr9-84893781-G-T

Variant summary

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

The NM_006180.6(NTRK2):​c.1633+26350G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.862 in 152,194 control chromosomes in the GnomAD database, including 56,674 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 0.86 (56674 hom., cov: 31)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1633+26350G>T		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1633+26350G>T		intron_variant		1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131067 AN: 152076 Hom.: 56633 Cov.: 31

Gnomad AFR AF: 0.924

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.818

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.862 AC: 131163 AN: 152194 Hom.: 56674 Cov.: 31 AF XY: 0.861 AC XY: 64085 AN XY: 74392

Gnomad4 AFR AF: 0.924

Gnomad4 AMR AF: 0.864

Gnomad4 ASJ AF: 0.818

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.844

Alfa AF: 0.845 Hom.: 7895

Bravo AF: 0.866

Asia WGS AF: 0.847 AC: 2945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.49

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: rs10868236; hg19: chr9-87508696; COSMIC: COSV99452080;