rs2749894
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001376.5(DYNC1H1):c.3015+18C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000299 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 0 hom. )
Consequence
DYNC1H1
NM_001376.5 intron
NM_001376.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.11
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 14-101991691-C-G is Benign according to our data. Variant chr14-101991691-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 668740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00152 (231/152128) while in subpopulation AFR AF= 0.00536 (222/41456). AF 95% confidence interval is 0.00478. There are 0 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 231 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYNC1H1 | NM_001376.5 | c.3015+18C>G | intron_variant | ENST00000360184.10 | NP_001367.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYNC1H1 | ENST00000360184.10 | c.3015+18C>G | intron_variant | 1 | NM_001376.5 | ENSP00000348965 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00153 AC: 233AN: 152010Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000446 AC: 112AN: 251236Hom.: 0 AF XY: 0.000383 AC XY: 52AN XY: 135838
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GnomAD4 exome AF: 0.000172 AC: 251AN: 1461780Hom.: 0 Cov.: 33 AF XY: 0.000140 AC XY: 102AN XY: 727198
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GnomAD4 genome AF: 0.00152 AC: 231AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.00155 AC XY: 115AN XY: 74384
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 02, 2018 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Dec 12, 2020 | - - |
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Charcot-Marie-Tooth disease axonal type 2O Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Charcot-Marie-Tooth disease axonal type 2O;C3281202:Intellectual disability, autosomal dominant 13;C5780022:Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 13, 2022 | - - |
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