rs35669708
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PM1PM5BP4_StrongBP6BS2
The NM_002529.4(NTRK1):c.2339G>A(p.Arg780Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,611,386 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R780P) has been classified as Pathogenic.
Frequency
Consequence
NM_002529.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NTRK1 | NM_002529.4 | c.2339G>A | p.Arg780Gln | missense_variant | 17/17 | ENST00000524377.7 | |
NTRK1 | NM_001012331.2 | c.2321G>A | p.Arg774Gln | missense_variant | 16/16 | ||
NTRK1 | NM_001007792.1 | c.2231G>A | p.Arg744Gln | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NTRK1 | ENST00000524377.7 | c.2339G>A | p.Arg780Gln | missense_variant | 17/17 | 1 | NM_002529.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00434 AC: 660AN: 152238Hom.: 7 Cov.: 33
GnomAD3 exomes AF: 0.00480 AC: 1166AN: 243110Hom.: 10 AF XY: 0.00537 AC XY: 710AN XY: 132246
GnomAD4 exome AF: 0.00583 AC: 8513AN: 1459030Hom.: 36 Cov.: 31 AF XY: 0.00613 AC XY: 4449AN XY: 725604
GnomAD4 genome ? AF: 0.00433 AC: 659AN: 152356Hom.: 7 Cov.: 33 AF XY: 0.00438 AC XY: 326AN XY: 74496
ClinVar
Submissions by phenotype
Hereditary insensitivity to pain with anhidrosis Uncertain:1Benign:5
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Likely benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | May 18, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Counsyl | Mar 06, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jan 07, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | NTRK1: PM5, BP4, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 02, 2018 | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 18, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
NTRK1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 11, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at