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NM_004082.5(DCTN1):c.376G>A (p.Ala126Thr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 30, 2016
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:
RCV000553770.9

Allele description [Variation Report for NM_004082.5(DCTN1):c.376G>A (p.Ala126Thr)]

NM_004082.5(DCTN1):c.376G>A (p.Ala126Thr)

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.376G>A (p.Ala126Thr)
HGVS:
  • NC_000002.12:g.74377449C>T
  • NG_008735.2:g.19639G>A
  • NM_001135040.3:c.376G>A
  • NM_001190836.2:c.325G>A
  • NM_001190837.2:c.376G>A
  • NM_001378991.1:c.325G>A
  • NM_001378992.1:c.325G>A
  • NM_004082.5:c.376G>AMANE SELECT
  • NP_001128512.1:p.Ala126Thr
  • NP_001177765.1:p.Ala109Thr
  • NP_001177766.1:p.Ala126Thr
  • NP_001365920.1:p.Ala109Thr
  • NP_001365921.1:p.Ala109Thr
  • NP_004073.2:p.Ala126Thr
  • NP_004073.2:p.Ala126Thr
  • LRG_237t1:c.376G>A
  • LRG_237:g.19639G>A
  • LRG_237p1:p.Ala126Thr
  • NC_000002.11:g.74604576C>T
  • NM_004082.4:c.376G>A
  • NR_033935.2:n.416G>A
Protein change:
A109T
Links:
dbSNP: rs1553466338
NCBI 1000 Genomes Browser:
rs1553466338
Molecular consequence:
  • NM_001135040.3:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001190836.2:c.325G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001190837.2:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378991.1:c.325G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378992.1:c.325G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004082.5:c.376G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_033935.2:n.416G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000644827Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 30, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

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, SCV000644827.5

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

Description

This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DCTN1-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies.The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. This sequence change replaces alanine with threonine at codon 126 of the DCTN1 protein (p.Ala126Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine.

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

Last Updated: Sep 29, 2024