rs1211166

Variant names:

• chr9-84671077-G-A
• rs1211166
• NM_006180.6:c.212+117G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84671077-G-A
• chr9-84671077-G-C
• chr9-84671077-G-T

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.212+117G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 959,496 control chromosomes in the GnomAD database, including 303,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.77 (45543 hom., cov: 34)
  • Exomes 𝑓: 0.80 (257665 hom.)
• Consequence: NTRK2 NM_006180.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.912
• Publications: 14 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=-0.88).
• BP6: Variant 9-84671077-G-A is Benign according to our data. Variant chr9-84671077-G-A is described in ClinVar as Benign. ClinVar VariationId is 1178699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.798 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.212+117G>A		intron	N/A	NP_006171.2
	NTRK2	NM_001018064.3		c.212+117G>A		intron	N/A	NP_001018074.1
	NTRK2	NM_001369532.1		c.212+117G>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.212+117G>A		intron	N/A	ENSP00000277120.3
	NTRK2	ENST00000323115.11	TSL:1	c.212+117G>A		intron	N/A	ENSP00000314586.5
	NTRK2	ENST00000304053.11	TSL:1	c.212+117G>A		intron	N/A	ENSP00000306167.7

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117320 AN: 152074 Hom.: 45509 Cov.: 34

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.884

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.835

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.804

Gnomad OTH AF: 0.789

GnomAD4 exome AF: 0.798 AC: 643829 AN: 807304 Hom.: 257665 AF XY: 0.795 AC XY: 334777 AN XY: 420844

African (AFR) AF: 0.688 AC: 14144 AN: 20564

American (AMR) AF: 0.819 AC: 28792 AN: 35154

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 17158 AN: 21578

East Asian (EAS) AF: 0.766 AC: 25612 AN: 33422

South Asian (SAS) AF: 0.746 AC: 50144 AN: 67230

European-Finnish (FIN) AF: 0.824 AC: 28646 AN: 34744

Middle Eastern (MID) AF: 0.766 AC: 2550 AN: 3330

European-Non Finnish (NFE) AF: 0.807 AC: 445743 AN: 552248

Other (OTH) AF: 0.795 AC: 31040 AN: 39034

GnomAD4 genome AF: 0.771 AC: 117409 AN: 152192 Hom.: 45543 Cov.: 34 AF XY: 0.773 AC XY: 57520 AN XY: 74394

African (AFR) AF: 0.688 AC: 28580 AN: 41530

American (AMR) AF: 0.797 AC: 12192 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2723 AN: 3468

East Asian (EAS) AF: 0.789 AC: 4067 AN: 5156

South Asian (SAS) AF: 0.752 AC: 3622 AN: 4818

European-Finnish (FIN) AF: 0.835 AC: 8854 AN: 10608

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.804 AC: 54676 AN: 67998

Other (OTH) AF: 0.786 AC: 1662 AN: 2114

Alfa AF: 0.747 Hom.: 9821

Bravo AF: 0.766

Asia WGS AF: 0.739 AC: 2572 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.7
DANN	Benign	0.44
PhyloP100		0.91
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: rs1211166; hg19: chr9-87285992;