rs10780691

Positions:

• chr9-84876338-C-T

Variant summary

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

The NM_001018065.2(NTRK2):​c.*4521C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,049,362 control chromosomes in the GnomAD database, including 126,204 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 0.39 (13186 hom., cov: 32)
  • Exomes 𝑓: 0.50 (113018 hom.)
• Consequence: NTRK2 NM_001018065.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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]

NTRK2 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1633+8907C>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+8907C>T		intron_variant		1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59580 AN: 151910 Hom.: 13183 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.497 AC: 446146 AN: 897334 Hom.: 113018 Cov.: 29 AF XY: 0.498 AC XY: 206380 AN XY: 414474

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.438

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.462

GnomAD4 genome AF: 0.392 AC: 59598 AN: 152028 Hom.: 13186 Cov.: 32 AF XY: 0.391 AC XY: 29019 AN XY: 74306

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.407

Alfa AF: 0.487 Hom.: 31184

Bravo AF: 0.378

Asia WGS AF: 0.352 AC: 1226 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	1.4
DANN	Benign	0.70

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: rs10780691; hg19: chr9-87491253; COSMIC: COSV99452061;