rs1624327

Positions:

• chr9-84814375-A-G

Variant summary

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

The NM_001007097.3(NTRK2):​c.*3796A>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 0.713 in 1,065,262 control chromosomes in the GnomAD database, including 271,531 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 0.71 (38642 hom., cov: 33)
  • Exomes 𝑓: 0.71 (232889 hom.)
• Consequence: NTRK2 NM_001007097.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1397-46665A>G		intron_variant		ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1397-46665A>G		intron_variant		1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107980 AN: 152066 Hom.: 38609 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.745

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.714 AC: 651669 AN: 913078 Hom.: 232889 Cov.: 43 AF XY: 0.714 AC XY: 300918 AN XY: 421494

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.717

Gnomad4 ASJ exome AF: 0.678

Gnomad4 EAS exome AF: 0.879

Gnomad4 SAS exome AF: 0.799

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.711

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.710 AC: 108067 AN: 152184 Hom.: 38642 Cov.: 33 AF XY: 0.715 AC XY: 53168 AN XY: 74398

Gnomad4 AFR AF: 0.643

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.865

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.745

Gnomad4 NFE AF: 0.725

Gnomad4 OTH AF: 0.703

Alfa AF: 0.722 Hom.: 39190

Bravo AF: 0.702

Asia WGS AF: 0.782 AC: 2718 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.84
DANN	Benign	0.57

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: rs1624327; hg19: chr9-87429290; COSMIC: COSV99451992;