rs7038236

Variant names:

• chr9-84873487-C-A
• rs7038236
• ENST00000304053.11:c.*1670C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-84873487-C-A
• chr9-84873487-C-T

Variant summary

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

The ENST00000304053.11(NTRK2):​c.*1670C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,058,988 control chromosomes in the GnomAD database, including 15,489 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 0.18 (2671 hom., cov: 32)
  • Exomes 𝑓: 0.17 (12818 hom.)
• Consequence: NTRK2 ENST00000304053.11 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.592
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1633+6056C>A		intron_variant	Intron 14 of 18	ENST00000277120.8	NP_006171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK2	ENST00000277120.8	c.1633+6056C>A		intron_variant	Intron 14 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27561 AN: 151812 Hom.: 2668 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0492

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.182

GnomAD4 exome AF: 0.166 AC: 150696 AN: 907058 Hom.: 12818 Cov.: 33 AF XY: 0.166 AC XY: 69482 AN XY: 418924

African (AFR) AF: 0.243 AC: 4684 AN: 19238

American (AMR) AF: 0.167 AC: 544 AN: 3254

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 1486 AN: 9834

East Asian (EAS) AF: 0.0375 AC: 536 AN: 14308

South Asian (SAS) AF: 0.157 AC: 2682 AN: 17100

European-Finnish (FIN) AF: 0.119 AC: 39 AN: 328

Middle Eastern (MID) AF: 0.127 AC: 263 AN: 2068

European-Non Finnish (NFE) AF: 0.167 AC: 134672 AN: 807434

Other (OTH) AF: 0.173 AC: 5790 AN: 33494

GnomAD4 genome AF: 0.182 AC: 27587 AN: 151930 Hom.: 2671 Cov.: 32 AF XY: 0.179 AC XY: 13319 AN XY: 74252

African (AFR) AF: 0.245 AC: 10122 AN: 41366

American (AMR) AF: 0.196 AC: 2997 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3468

East Asian (EAS) AF: 0.0495 AC: 256 AN: 5168

South Asian (SAS) AF: 0.151 AC: 727 AN: 4808

European-Finnish (FIN) AF: 0.127 AC: 1340 AN: 10558

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.163 AC: 11053 AN: 67970

Other (OTH) AF: 0.180 AC: 379 AN: 2108

Alfa AF: 0.133 Hom.: 394

Bravo AF: 0.187

Asia WGS AF: 0.103 AC: 359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.48
PhyloP100		0.59
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: rs7038236; hg19: chr9-87488402;