rs7020204

Variant names:

• chr9-84811272-C-T
• rs7020204
• ENST00000359847.4:c.*693C>T

Variant summary

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

The ENST00000359847.4(NTRK2):​c.*693C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 1,064,048 control chromosomes in the GnomAD database, including 4,286 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 0.097 (788 hom., cov: 32)
  • Exomes 𝑓: 0.086 (3498 hom.)
• Consequence: NTRK2 ENST00000359847.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.540
• Publications: 11 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK2	NM_006180.6	c.1397-49768C>T		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.1397-49768C>T		intron_variant	Intron 12 of 18	1	NM_006180.6	ENSP00000277120.3

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14748 AN: 151622 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0855 AC: 78039 AN: 912308 Hom.: 3498 Cov.: 33 AF XY: 0.0852 AC XY: 35903 AN XY: 421174

African (AFR) AF: 0.0959 AC: 1881 AN: 19618

American (AMR) AF: 0.134 AC: 462 AN: 3442

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 1018 AN: 10208

East Asian (EAS) AF: 0.167 AC: 2466 AN: 14792

South Asian (SAS) AF: 0.102 AC: 1751 AN: 17132

European-Finnish (FIN) AF: 0.0613 AC: 25 AN: 408

Middle Eastern (MID) AF: 0.105 AC: 221 AN: 2108

European-Non Finnish (NFE) AF: 0.0826 AC: 66949 AN: 810634

Other (OTH) AF: 0.0962 AC: 3266 AN: 33966

GnomAD4 genome AF: 0.0973 AC: 14762 AN: 151740 Hom.: 788 Cov.: 32 AF XY: 0.0998 AC XY: 7399 AN XY: 74114

African (AFR) AF: 0.0984 AC: 4064 AN: 41320

American (AMR) AF: 0.149 AC: 2265 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.173 AC: 889 AN: 5152

South Asian (SAS) AF: 0.117 AC: 563 AN: 4796

European-Finnish (FIN) AF: 0.0767 AC: 805 AN: 10500

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5460 AN: 67970

Other (OTH) AF: 0.106 AC: 224 AN: 2106

Alfa AF: 0.0878 Hom.: 259

Bravo AF: 0.101

Asia WGS AF: 0.153 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.2
DANN	Benign	0.76
PhyloP100		0.54
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: rs7020204; hg19: chr9-87426187;