rs2289656

Variant names:

• chr9-84948647-G-A
• rs2289656
• NM_006180.6:c.1937+13G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84948647-G-A
• chr9-84948647-G-C
• chr9-84948647-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006180.6(NTRK2):​c.1937+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,612,644 control chromosomes in the GnomAD database, including 24,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1953 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22225 hom.)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.26

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-84948647-G-A is Benign according to our data. Variant chr9-84948647-G-A is described in ClinVar as [Benign]. Clinvar id is 1249612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1937+13G>A		intron_variant	Intron 16 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1937+13G>A		intron_variant	Intron 16 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23329 AN: 152072 Hom.: 1956 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.0913

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.150 AC: 37451 AN: 249854 AF XY: 0.151

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.125

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.0332

Gnomad FIN exome AF: 0.166

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.172

GnomAD4 exome AF: 0.170 AC: 247774 AN: 1460454 Hom.: 22225 Cov.: 33 AF XY: 0.169 AC XY: 122517 AN XY: 726502

Gnomad4 AFR exome AF: 0.109 AC: 3643 AN: 33464

Gnomad4 AMR exome AF: 0.127 AC: 5668 AN: 44668

Gnomad4 ASJ exome AF: 0.242 AC: 6337 AN: 26134

Gnomad4 EAS exome AF: 0.0378 AC: 1500 AN: 39694

Gnomad4 SAS exome AF: 0.103 AC: 8877 AN: 86168

Gnomad4 FIN exome AF: 0.162 AC: 8619 AN: 53368

Gnomad4 NFE exome AF: 0.182 AC: 201931 AN: 1110856

Gnomad4 Remaining exome AF: 0.165 AC: 9930 AN: 60338

GnomAD4 genome AF: 0.153 AC: 23328 AN: 152190 Hom.: 1953 Cov.: 32 AF XY: 0.151 AC XY: 11241 AN XY: 74392

Gnomad4 AFR AF: 0.111 AC: 0.110827 AN: 0.110827

Gnomad4 AMR AF: 0.148 AC: 0.147574 AN: 0.147574

Gnomad4 ASJ AF: 0.248 AC: 0.247839 AN: 0.247839

Gnomad4 EAS AF: 0.0354 AC: 0.0353555 AN: 0.0353555

Gnomad4 SAS AF: 0.0916 AC: 0.0915698 AN: 0.0915698

Gnomad4 FIN AF: 0.171 AC: 0.171008 AN: 0.171008

Gnomad4 NFE AF: 0.185 AC: 0.185213 AN: 0.185213

Gnomad4 OTH AF: 0.164 AC: 0.163516 AN: 0.163516

Alfa AF: 0.172 Hom.: 6847

Bravo AF: 0.150

Asia WGS AF: 0.0910 AC: 319 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Sep 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Obesity, hyperphagia, and developmental delay Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Developmental and epileptic encephalopathy, 58 Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.096
DANN	Benign	0.59
Mutation Taster		=100/0	polymorphism (auto)

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: rs2289656; hg19: chr9-87563562; COSMIC: COSV52852599;