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NM_004082.5(DCTN1):c.395G>A (p.Arg132Gln) AND Neuronopathy, distal hereditary motor, type 7B

Germline classification:
Uncertain significance (1 submission)
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:
RCV001174528.2

Allele description [Variation Report for NM_004082.5(DCTN1):c.395G>A (p.Arg132Gln)]

NM_004082.5(DCTN1):c.395G>A (p.Arg132Gln)

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.395G>A (p.Arg132Gln)
HGVS:
  • NC_000002.12:g.74376761C>T
  • NG_008735.2:g.20327G>A
  • NM_001135040.3:c.393+671G>A
  • NM_001190836.2:c.342+671G>A
  • NM_001190837.2:c.393+671G>A
  • NM_001378991.1:c.344G>A
  • NM_001378992.1:c.344G>A
  • NM_004082.5:c.395G>AMANE SELECT
  • NP_001365920.1:p.Arg115Gln
  • NP_001365921.1:p.Arg115Gln
  • NP_004073.2:p.Arg132Gln
  • LRG_237t1:c.395G>A
  • LRG_237:g.20327G>A
  • NC_000002.11:g.74603888C>T
  • NC_000002.11:g.74603888C>T
  • NM_004082.4:c.395G>A
Protein change:
R115Q
Links:
dbSNP: rs753892865
NCBI 1000 Genomes Browser:
rs753892865
Molecular consequence:
  • NM_001135040.3:c.393+671G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001190836.2:c.342+671G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001190837.2:c.393+671G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001378991.1:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378992.1:c.344G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004082.5:c.395G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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
SCV001245433Institute of Human Genetics, University of Goettingen
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significanceunknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Non-Finnish Europeanunknownunknown1not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Institute of Human Genetics, University of Goettingen, SCV001245433.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Non-Finnish European1not providednot providedclinical testing PubMed (1)

Description

Although there are 7 individuals harbouring the DCTN1 variant c.395G>A in the gnomAD database and one individual in the ExAC database there is still little known about the penetrance of pathogenic DCTN1 mutations. To our knowledge, this mutation is not located within a functional domain of the protein. The affected nucleotide is highly conserved, the affected amino acid (considering 10 species) is moderately conserved and there is a small physicochemical difference between Arg and Gln. Prediction programs do not provide a clear computational verdict on the pathogenicity of this variant and its effect on the nearest splice site. ACMG criteria used for classification: PM2, PP3 (considering three pathogenic predictions from M-CAP, PolyPhen-2 and MutationTaster vs. one benign prediction from SIFT). Thus, this DCTN1 variant is classified by our Institute as a variant of unknown significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024