rs1187323

Positions:

• chr9-84668501-C-A
• chr9-84668501-C-G
• chr9-84668501-C-T

Variant summary

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

The ENST00000686259.1(NTRK2):​c.-866C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,202 control chromosomes in the GnomAD database, including 49,132 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 0.80 (49131 hom., cov: 34)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: NTRK2 ENST00000686259.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_001007097.3			upstream_gene_variant			NP_001007098.1
NTRK2	NM_001018066.3			upstream_gene_variant			NP_001018076.1
NTRK2	NM_001291937.2			upstream_gene_variant			NP_001278866.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000686259.1	c.-866C>A		5_prime_UTR_variant	1/19			ENSP00000509743	A1
NTRK2	ENST00000686496.1	c.-1321C>A		5_prime_UTR_variant	1/20			ENSP00000510060	A1
NTRK2	ENST00000686542.1	c.-988C>A		5_prime_UTR_variant	1/15			ENSP00000510356

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122086 AN: 152078 Hom.: 49093 Cov.: 34

Gnomad AFR AF: 0.795

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.805

Gnomad OTH AF: 0.813

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 3 AN XY: 6

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.803 AC: 122181 AN: 152194 Hom.: 49131 Cov.: 34 AF XY: 0.803 AC XY: 59786 AN XY: 74408

Gnomad4 AFR AF: 0.795

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.785

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.752

Gnomad4 FIN AF: 0.835

Gnomad4 NFE AF: 0.805

Gnomad4 OTH AF: 0.810

Alfa AF: 0.796 Hom.: 18657

Bravo AF: 0.801

Asia WGS AF: 0.750 AC: 2610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	14
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1187323; hg19: chr9-87283416;