rs121909344
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2
The NM_004082.5(DCTN1):c.2353C>T(p.Arg785Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000256 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004082.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000191 AC: 29AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000195 AC: 49AN: 251444Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135900
GnomAD4 exome AF: 0.000263 AC: 385AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.000239 AC XY: 174AN XY: 727246
GnomAD4 genome AF: 0.000191 AC: 29AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74346
ClinVar
Submissions by phenotype
not provided Uncertain:4
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Reported previously in a patient with apparently sporadic ALS; however, no further clinical or family history information was provided (Mehta et al., 2019); Reported previously as a variant of uncertain significance in a patient with ALS; however, no further clinical or segregation information was provided (Shepheard et al., 2021); Reported previously in two siblings with probable ALS (one with upper limb onset and one with bulbar onset), and also seen in two unaffected family members (Mnch et al., 2004); Reported previously in a patient with ALS (further clinical information not provided) and in one control sample (Morgan et al., 2017); Published functional studies show that this variant does not have major differences in cell morphology (Stockmann et al., 2013; Dixit R et al., 2008); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23447461, 23143281, 33924373, 20349096, 17911166, 31291987, 28235672, 28625595, 16765570, 17593875, 37168679, 19506225, 28792508, 26662454, 25025039, 25109764, 30270202, 33589474, 15326253, 28430856, 18812314) -
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Perry syndrome Uncertain:2
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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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Neuronopathy, distal hereditary motor, type 7B;C1862939:Amyotrophic lateral sclerosis type 1;C1868594:Perry syndrome Uncertain:1Benign:1
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Charcot-Marie-Tooth disease Uncertain:1
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Neuronopathy, distal hereditary motor, type 7B Uncertain:1
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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. -
Amyotrophic lateral sclerosis type 1 Uncertain:1
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
DCTN1-related disorder Benign:1
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). -
Amyotrophic lateral sclerosis, susceptibility to Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at