rs200952455
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_004082.5(DCTN1):c.999C>T(p.Asp333=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000861 in 1,614,154 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 5 hom. )
Consequence
DCTN1
NM_004082.5 synonymous
NM_004082.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.05
Genes affected
DCTN1 (HGNC:2711): (dynactin subunit 1) This gene encodes the largest subunit of dynactin, a macromolecular complex consisting of 10 subunits ranging in size from 22 to 150 kD. Dynactin binds to both microtubules and cytoplasmic dynein. Dynactin is involved in a diverse array of cellular functions, including ER-to-Golgi transport, the centripetal movement of lysosomes and endosomes, spindle formation, chromosome movement, nuclear positioning, and axonogenesis. This subunit interacts with dynein intermediate chain by its domains directly binding to dynein and binds to microtubules via a highly conserved glycine-rich cytoskeleton-associated protein (CAP-Gly) domain in its N-terminus. Alternative splicing of this gene results in multiple transcript variants encoding distinct isoforms. Mutations in this gene cause distal hereditary motor neuronopathy type VIIB (HMN7B) which is also known as distal spinal and bulbar muscular atrophy (dSBMA). [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 2-74370670-G-A is Benign according to our data. Variant chr2-74370670-G-A is described in ClinVar as [Benign]. Clinvar id is 771985.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-74370670-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-4.05 with no splicing effect.
BS2
?
High AC in GnomAd4 at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCTN1 | NM_004082.5 | c.999C>T | p.Asp333= | synonymous_variant | 10/32 | ENST00000628224.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCTN1 | ENST00000628224.3 | c.999C>T | p.Asp333= | synonymous_variant | 10/32 | 5 | NM_004082.5 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152156Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000175 AC: 44AN: 251458Hom.: 0 AF XY: 0.000243 AC XY: 33AN XY: 135912
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GnomAD4 exome AF: 0.0000841 AC: 123AN: 1461880Hom.: 5 Cov.: 34 AF XY: 0.000116 AC XY: 84AN XY: 727242
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152274Hom.: 1 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74458
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Neuronopathy, distal hereditary motor, type 7B;C1862939:Amyotrophic lateral sclerosis type 1;C1868594:Perry syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 30, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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