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NM_004082.5(DCTN1):c.3530-1G>A AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 22, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001879545.6

Allele description [Variation Report for NM_004082.5(DCTN1):c.3530-1G>A]

NM_004082.5(DCTN1):c.3530-1G>A

Gene:
DCTN1:dynactin subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p13.1
Genomic location:
Preferred name:
NM_004082.5(DCTN1):c.3530-1G>A
HGVS:
  • NC_000002.12:g.74362730C>T
  • NG_008735.2:g.34358G>A
  • NM_001135040.3:c.3455-1G>A
  • NM_001135041.3:c.3113-1G>A
  • NM_001190836.2:c.3404-1G>A
  • NM_001190837.2:c.3509-1G>A
  • NM_001378991.1:c.3479-1G>A
  • NM_001378992.1:c.3461-1G>A
  • NM_004082.5:c.3530-1G>AMANE SELECT
  • NM_023019.4:c.3128-1G>A
  • LRG_237:g.34358G>A
  • NC_000002.11:g.74589857C>T
Links:
dbSNP: rs2104393432
NCBI 1000 Genomes Browser:
rs2104393432
Molecular consequence:
  • NM_001135040.3:c.3455-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001135041.3:c.3113-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001190836.2:c.3404-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001190837.2:c.3509-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001378991.1:c.3479-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001378992.1:c.3461-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_004082.5:c.3530-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_023019.4:c.3128-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Amyotrophic lateral sclerosis type 1 (ALS1)
Synonyms:
AMYOTROPHIC LATERAL SCLEROSIS 1, FAMILIAL
Identifiers:
MONDO: MONDO:0007103; MedGen: C1862939; Orphanet: 803; OMIM: 105400
Name:
Perry syndrome
Synonyms:
Parkinsonism with alveolar hypoventilation and mental depression
Identifiers:
MONDO: MONDO:0008201; MedGen: C1868594; Orphanet: 178509; OMIM: 168605
Name:
Neuronopathy, distal hereditary motor, type 7B
Synonyms:
HMN VIIB; LOWER MOTOR NEURON DISEASE, DYNACTIN TYPE; NEURONOPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL DOMINANT 14; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011879; MedGen: C1843315; Orphanet: 139589; OMIM: 607641

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002137788Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Feb 22, 2021)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002137788.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change affects an acceptor splice site in intron 29 of the DCTN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in DCTN1 cause disease. This variant is not present in population databases (ExAC no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with DCTN1-related conditions.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024