rs1387923

chr9-85025721-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.*4284A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 232,770 control chromosomes in the GnomAD database, including 28,159 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 0.47 (17559 hom., cov: 32)
  • Exomes 𝑓: 0.50 (10600 hom.)
• Consequence: NTRK2 NM_006180.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK2	NM_006180.6	c.*4284A>G		3_prime_UTR_variant	19/19	ENST00000277120.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK2	ENST00000277120.8	c.*4284A>G		3_prime_UTR_variant	19/19	1	NM_006180.6	P3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71383 AN: 151818 Hom.: 17556 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.556

Gnomad OTH AF: 0.497

GnomAD4 exome AF: 0.496 AC: 40092 AN: 80834 Hom.: 10600 Cov.: 0 AF XY: 0.499 AC XY: 18523 AN XY: 37148

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.447

Gnomad4 ASJ exome AF: 0.562

Gnomad4 EAS exome AF: 0.188

Gnomad4 SAS exome AF: 0.516

Gnomad4 FIN exome AF: 0.483

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.470 AC: 71410 AN: 151936 Hom.: 17559 Cov.: 32 AF XY: 0.464 AC XY: 34468 AN XY: 74246

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.556

Gnomad4 OTH AF: 0.497

Alfa AF: 0.496 Hom.: 3641

Bravo AF: 0.458

Asia WGS AF: 0.461 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.61
Dann	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1387923; hg19: chr9-87640636;