NM_006180.6:c.1396+27832G>A

Variant names:

• chr9-84779917-G-A
• rs12555159
• NM_006180.6:c.1396+27832G>A

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+27832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 152,098 control chromosomes in the GnomAD database, including 946 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 0.084 (946 hom., cov: 32)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.769
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1396+27832G>A		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+27832G>A		intron_variant	Intron 12 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.0834 AC: 12675 AN: 151980 Hom.: 933 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0590

Gnomad SAS AF: 0.0334

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0654

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

GnomAD4 genome AF: 0.0837 AC: 12730 AN: 152098 Hom.: 946 Cov.: 32 AF XY: 0.0827 AC XY: 6149 AN XY: 74378

African (AFR) AF: 0.192 AC: 7978 AN: 41446

American (AMR) AF: 0.0764 AC: 1167 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.0590 AC: 305 AN: 5172

South Asian (SAS) AF: 0.0335 AC: 161 AN: 4810

European-Finnish (FIN) AF: 0.0350 AC: 371 AN: 10596

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0356 AC: 2419 AN: 68002

Other (OTH) AF: 0.0718 AC: 152 AN: 2116

Alfa AF: 0.0704 Hom.: 89

Bravo AF: 0.0929

Asia WGS AF: 0.0760 AC: 264 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.3
DANN	Benign	0.37
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: rs12555159; hg19: chr9-87394832;