rs1573219

Variant names:

• chr9-84772707-A-G
• rs1573219
• NM_006180.6:c.1396+20622A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-84772707-A-G
• chr9-84772707-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006180.6(NTRK2):​c.1396+20622A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,000 control chromosomes in the GnomAD database, including 34,677 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 0.67 (34677 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1396+20622A>G		intron_variant	Intron 12 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1396+20622A>G		intron_variant	Intron 12 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101833 AN: 151882 Hom.: 34675 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.670 AC: 101881 AN: 152000 Hom.: 34677 Cov.: 32 AF XY: 0.675 AC XY: 50125 AN XY: 74306

African (AFR) AF: 0.568 AC: 23550 AN: 41432

American (AMR) AF: 0.693 AC: 10574 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2343 AN: 3462

East Asian (EAS) AF: 0.739 AC: 3813 AN: 5158

South Asian (SAS) AF: 0.716 AC: 3449 AN: 4814

European-Finnish (FIN) AF: 0.777 AC: 8215 AN: 10572

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.702 AC: 47694 AN: 67980

Other (OTH) AF: 0.670 AC: 1414 AN: 2112

Alfa AF: 0.685 Hom.: 101808

Bravo AF: 0.658

Asia WGS AF: 0.694 AC: 2410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.75
PhyloP100		-0.77
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: rs1573219; hg19: chr9-87387622;