rs1490403

Positions:

• chr9-85023591-T-A

Variant summary

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

The NM_006180.6(NTRK2):​c.*2154T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 224,384 control chromosomes in the GnomAD database, including 58,903 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 0.74 (41976 hom., cov: 28)
  • Exomes 𝑓: 0.67 (16927 hom.)
• Consequence: NTRK2 NM_006180.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.397

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 = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.*2154T>A		3_prime_UTR_variant	19/19	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.*2154T>A		3_prime_UTR_variant	19/19	1	NM_006180.6	ENSP00000277120	P3

Frequencies

GnomAD3 genomes AF: 0.737 AC: 111702 AN: 151578 Hom.: 41932 Cov.: 28

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.723

Gnomad OTH AF: 0.739

GnomAD4 exome AF: 0.666 AC: 48416 AN: 72688 Hom.: 16927 Cov.: 0 AF XY: 0.668 AC XY: 22407 AN XY: 33540

Gnomad4 AFR exome AF: 0.840

Gnomad4 AMR exome AF: 0.740

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.313

Gnomad4 SAS exome AF: 0.703

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.737 AC: 111804 AN: 151696 Hom.: 41976 Cov.: 28 AF XY: 0.727 AC XY: 53840 AN XY: 74100

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.723

Gnomad4 OTH AF: 0.740

Alfa AF: 0.732 Hom.: 5081

Bravo AF: 0.748

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.28
DANN	Benign	0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1490403; hg19: chr9-87638506;