rs1778929

Variant names:

• chr9-84707625-T-C
• rs1778929
• NM_006180.6:c.360-219T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006180.6(NTRK2):​c.360-219T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,870 control chromosomes in the GnomAD database, including 19,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (19687 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.221
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 58

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• obesity, hyperphagia, and developmental delay

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-84707625-T-C is Benign according to our data. Variant chr9-84707625-T-C is described in ClinVar as Benign. ClinVar VariationId is 1266582.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.360-219T>C		intron_variant	Intron 4 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.360-219T>C		intron_variant	Intron 4 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76755 AN: 151752 Hom.: 19688 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.506 AC: 76776 AN: 151870 Hom.: 19687 Cov.: 32 AF XY: 0.510 AC XY: 37884 AN XY: 74234

African (AFR) AF: 0.431 AC: 17852 AN: 41402

American (AMR) AF: 0.556 AC: 8481 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3468

East Asian (EAS) AF: 0.594 AC: 3066 AN: 5164

South Asian (SAS) AF: 0.558 AC: 2685 AN: 4810

European-Finnish (FIN) AF: 0.573 AC: 6023 AN: 10514

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35407 AN: 67942

Other (OTH) AF: 0.495 AC: 1045 AN: 2112

Alfa AF: 0.507 Hom.: 5612

Bravo AF: 0.498

Asia WGS AF: 0.506 AC: 1753 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

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	1.4
DANN	Benign	0.68
PhyloP100		-0.22
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

Other links and lift over

dbSNP: rs1778929; hg19: chr9-87322540;