chr9-84811383-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000359847.4(NTRK2):​c.*804A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 1,065,824 control chromosomes in the GnomAD database, including 8,419 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 0.17 ( 3441 hom., cov: 32)
Exomes 𝑓: 0.093 ( 4978 hom. )

Consequence

NTRK2
ENST00000359847.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.286

Publications

17 publications found
Variant links:
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NTRK2NM_006180.6 linkc.1397-49657A>G intron_variant Intron 12 of 18 ENST00000277120.8 NP_006171.2 Q16620-4A0A024R230Q5VWE5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NTRK2ENST00000277120.8 linkc.1397-49657A>G intron_variant Intron 12 of 18 1 NM_006180.6 ENSP00000277120.3 Q16620-4

Frequencies

GnomAD3 genomes
AF:
0.173
AC:
26360
AN:
152070
Hom.:
3432
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.362
Gnomad AMI
AF:
0.139
Gnomad AMR
AF:
0.180
Gnomad ASJ
AF:
0.0975
Gnomad EAS
AF:
0.172
Gnomad SAS
AF:
0.117
Gnomad FIN
AF:
0.0766
Gnomad MID
AF:
0.139
Gnomad NFE
AF:
0.0815
Gnomad OTH
AF:
0.151
GnomAD4 exome
AF:
0.0934
AC:
85295
AN:
913636
Hom.:
4978
Cov.:
33
AF XY:
0.0925
AC XY:
39001
AN XY:
421726
show subpopulations
African (AFR)
AF:
0.373
AC:
7334
AN:
19654
American (AMR)
AF:
0.159
AC:
552
AN:
3474
Ashkenazi Jewish (ASJ)
AF:
0.100
AC:
1029
AN:
10246
East Asian (EAS)
AF:
0.168
AC:
2509
AN:
14940
South Asian (SAS)
AF:
0.102
AC:
1758
AN:
17154
European-Finnish (FIN)
AF:
0.0654
AC:
34
AN:
520
Middle Eastern (MID)
AF:
0.121
AC:
256
AN:
2110
European-Non Finnish (NFE)
AF:
0.0837
AC:
67921
AN:
811510
Other (OTH)
AF:
0.115
AC:
3902
AN:
34028
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.455
Heterozygous variant carriers
0
3970
7940
11910
15880
19850
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
3390
6780
10170
13560
16950
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.174
AC:
26412
AN:
152188
Hom.:
3441
Cov.:
32
AF XY:
0.173
AC XY:
12909
AN XY:
74418
show subpopulations
African (AFR)
AF:
0.362
AC:
15015
AN:
41466
American (AMR)
AF:
0.179
AC:
2746
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.0975
AC:
338
AN:
3468
East Asian (EAS)
AF:
0.172
AC:
890
AN:
5180
South Asian (SAS)
AF:
0.117
AC:
567
AN:
4828
European-Finnish (FIN)
AF:
0.0766
AC:
812
AN:
10602
Middle Eastern (MID)
AF:
0.136
AC:
40
AN:
294
European-Non Finnish (NFE)
AF:
0.0816
AC:
5548
AN:
68022
Other (OTH)
AF:
0.156
AC:
329
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1002
2003
3005
4006
5008
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
252
504
756
1008
1260
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.106
Hom.:
2062
Bravo
AF:
0.189
Asia WGS
AF:
0.176
AC:
611
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
1.1
DANN
Benign
0.55
PhyloP100
-0.29
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

Publications

Other links and lift over

dbSNP: rs2013566; hg19: chr9-87426298; API