rs2289656
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000277120.8(NTRK2):c.1937+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,612,644 control chromosomes in the GnomAD database, including 24,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.15 ( 1953 hom., cov: 32)
Exomes 𝑓: 0.17 ( 22225 hom. )
Consequence
NTRK2
ENST00000277120.8 intron
ENST00000277120.8 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.26
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 9-84948647-G-A is Benign according to our data. Variant chr9-84948647-G-A is described in ClinVar as [Benign]. Clinvar id is 1249612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NTRK2 | NM_006180.6 | c.1937+13G>A | intron_variant | ENST00000277120.8 | NP_006171.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NTRK2 | ENST00000277120.8 | c.1937+13G>A | intron_variant | 1 | NM_006180.6 | ENSP00000277120 | P3 |
Frequencies
GnomAD3 genomes AF: 0.153 AC: 23329AN: 152072Hom.: 1956 Cov.: 32
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GnomAD3 exomes AF: 0.150 AC: 37451AN: 249854Hom.: 3174 AF XY: 0.151 AC XY: 20363AN XY: 135024
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GnomAD4 exome AF: 0.170 AC: 247774AN: 1460454Hom.: 22225 Cov.: 33 AF XY: 0.169 AC XY: 122517AN XY: 726502
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GnomAD4 genome AF: 0.153 AC: 23328AN: 152190Hom.: 1953 Cov.: 32 AF XY: 0.151 AC XY: 11241AN XY: 74392
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 25, 2018 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Developmental and epileptic encephalopathy, 58 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Obesity, hyperphagia, and developmental delay Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at