9-84765636-C-G

Variant names:

• chr9-84765636-C-G
• rs7027979
• NM_006180.6:c.1396+13551C>G

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+13551C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,964 control chromosomes in the GnomAD database, including 26,894 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 0.58 (26894 hom., cov: 31)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• 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: Labcorp Genetics (formerly Invitae), G2P
• 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 (SAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006180.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	NM_006180.6	MANE Select	c.1396+13551C>G		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.1396+13551C>G		intron	N/A	NP_001018074.1	Q548C2
	NTRK2	NM_001369532.1		c.1396+13551C>G		intron	N/A	NP_001356461.1	Q16620-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.1396+13551C>G		intron	N/A	ENSP00000277120.3	Q16620-4
	NTRK2	ENST00000323115.11	TSL:1	c.1360+13551C>G		intron	N/A	ENSP00000314586.5	A0A8J8YUT9
	NTRK2	ENST00000304053.11	TSL:1	c.1396+13551C>G		intron	N/A	ENSP00000306167.7	Q16620-3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87611 AN: 151844 Hom.: 26912 Cov.: 31

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.576 AC: 87604 AN: 151964 Hom.: 26894 Cov.: 31 AF XY: 0.582 AC XY: 43189 AN XY: 74258

African (AFR) AF: 0.354 AC: 14666 AN: 41432

American (AMR) AF: 0.612 AC: 9338 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.658 AC: 2278 AN: 3462

East Asian (EAS) AF: 0.680 AC: 3500 AN: 5150

South Asian (SAS) AF: 0.682 AC: 3293 AN: 4828

European-Finnish (FIN) AF: 0.727 AC: 7667 AN: 10544

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44933 AN: 67964

Other (OTH) AF: 0.593 AC: 1251 AN: 2108

Alfa AF: 0.613 Hom.: 3682

Bravo AF: 0.555

Asia WGS AF: 0.616 AC: 2141 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.67
PhyloP100		-1.2
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: rs7027979; hg19: chr9-87380551;