rs13749
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001376.5(DYNC1H1):āc.13080T>Cā(p.Thr4360=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,613,124 control chromosomes in the GnomAD database, including 38,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.29 ( 9246 hom., cov: 29)
Exomes š: 0.18 ( 29237 hom. )
Consequence
DYNC1H1
NM_001376.5 synonymous
NM_001376.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.08
Genes affected
DYNC1H1 (HGNC:2961): (dynein cytoplasmic 1 heavy chain 1) Dyneins are a group of microtubule-activated ATPases that function as molecular motors. They are divided into two subgroups of axonemal and cytoplasmic dyneins. The cytoplasmic dyneins function in intracellular motility, including retrograde axonal transport, protein sorting, organelle movement, and spindle dynamics. Molecules of conventional cytoplasmic dynein are comprised of 2 heavy chain polypeptides and a number of intermediate and light chains.This gene encodes a member of the cytoplasmic dynein heavy chain family. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 14-102047890-T-C is Benign according to our data. Variant chr14-102047890-T-C is described in ClinVar as [Benign]. Clinvar id is 128929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102047890-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.08 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.13080T>C | p.Thr4360= | synonymous_variant | 73/78 | ENST00000360184.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.13080T>C | p.Thr4360= | synonymous_variant | 73/78 | 1 | NM_001376.5 | P1 | |
ENST00000553701.1 | n.346+2555A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.294 AC: 44567AN: 151360Hom.: 9216 Cov.: 29
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GnomAD3 exomes AF: 0.225 AC: 56385AN: 251050Hom.: 7987 AF XY: 0.217 AC XY: 29479AN XY: 135758
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GnomAD4 exome AF: 0.183 AC: 267168AN: 1461646Hom.: 29237 Cov.: 33 AF XY: 0.184 AC XY: 133540AN XY: 727132
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GnomAD4 genome ? AF: 0.295 AC: 44657AN: 151478Hom.: 9246 Cov.: 29 AF XY: 0.290 AC XY: 21458AN XY: 74068
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ClinVar
Significance: Benign
Submissions summary: Benign:15
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 25, 2013 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Charcot-Marie-Tooth disease axonal type 2O Benign:3
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Charcot-Marie-Tooth disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 08, 2016 | This alteration is classified as 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Autosomal dominant cerebellar ataxia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Intellectual disability, autosomal dominant 13 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 30, 2021 | - - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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