rs7048278

Variant names:

• chr9-84745238-G-A
• rs7048278
• NM_006180.6:c.1296+165G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84745238-G-A
• chr9-84745238-G-C

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.1296+165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 151,892 control chromosomes in the GnomAD database, including 28,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.60 (28114 hom., cov: 30)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.178
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 9-84745238-G-A is Benign according to our data. Variant chr9-84745238-G-A is described in ClinVar as Benign. ClinVar VariationId is 1266519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.662 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	NM_006180.6	MANE Select	c.1296+165G>A		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.1296+165G>A		intron	N/A	NP_001018074.1
	NTRK2	NM_001369532.1		c.1296+165G>A		intron	N/A	NP_001356461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK2	ENST00000277120.8	TSL:1 MANE Select	c.1296+165G>A		intron	N/A	ENSP00000277120.3
	NTRK2	ENST00000323115.11	TSL:1	c.1260+165G>A		intron	N/A	ENSP00000314586.5
	NTRK2	ENST00000304053.11	TSL:1	c.1296+165G>A		intron	N/A	ENSP00000306167.7

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90620 AN: 151774 Hom.: 28133 Cov.: 30

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.662

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.597 AC: 90606 AN: 151892 Hom.: 28114 Cov.: 30 AF XY: 0.601 AC XY: 44594 AN XY: 74204

African (AFR) AF: 0.421 AC: 17409 AN: 41388

American (AMR) AF: 0.622 AC: 9502 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.662 AC: 2294 AN: 3466

East Asian (EAS) AF: 0.675 AC: 3476 AN: 5152

South Asian (SAS) AF: 0.682 AC: 3273 AN: 4800

European-Finnish (FIN) AF: 0.728 AC: 7670 AN: 10534

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.663 AC: 45023 AN: 67954

Other (OTH) AF: 0.606 AC: 1280 AN: 2112

Alfa AF: 0.612 Hom.: 4419

Bravo AF: 0.578

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.57
PhyloP100		0.18
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: rs7048278; hg19: chr9-87360153;