rs3824519

Positions:

• chr9-84955089-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006180.6(NTRK2):​c.1938-194C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,224 control chromosomes in the GnomAD database, including 716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.090 (716 hom., cov: 33)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.79

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-84955089-C-T is Benign according to our data. Variant chr9-84955089-C-T is described in ClinVar as [Benign]. Clinvar id is 1269737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1938-194C>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.1938-194C>T		intron_variant		1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13726 AN: 152106 Hom.: 712 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0418

Gnomad FIN AF: 0.0512

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0903 AC: 13748 AN: 152224 Hom.: 716 Cov.: 33 AF XY: 0.0889 AC XY: 6615 AN XY: 74428

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0274

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0512

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0725 Hom.: 231

Bravo AF: 0.0981

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.21
DANN	Benign	0.54

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: rs3824519; hg19: chr9-87570004; COSMIC: COSV99453826;