NM_004082.5(DCTN1):c.2371T>C (p.Cys791Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 27, 2022
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:: RCV001057320.7

Allele description [Variation Report for NM_004082.5(DCTN1):c.2371T>C (p.Cys791Arg)]

NM_004082.5(DCTN1):c.2371T>C (p.Cys791Arg)

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.2371T>C (p.Cys791Arg)

Other names:

p.Cys791Arg

HGVS:

NC_000002.12:g.74366878A>G
NG_008735.2:g.30210T>C
NM_001135040.3:c.2311T>C
NM_001135041.3:c.1969T>C
NM_001190836.2:c.2260T>C
NM_001190837.2:c.2350T>C
NM_001378991.1:c.2320T>C
NM_001378992.1:c.2302T>C
NM_004082.5:c.2371T>CMANE SELECT
NM_023019.4:c.1969T>C
NP_001128512.1:p.Cys771Arg
NP_001128513.1:p.Cys657Arg
NP_001177765.1:p.Cys754Arg
NP_001177766.1:p.Cys784Arg
NP_001365920.1:p.Cys774Arg
NP_001365921.1:p.Cys768Arg
NP_004073.2:p.Cys791Arg
NP_004073.2:p.Cys791Arg
NP_075408.1:p.Cys657Arg
LRG_237t1:c.2371T>C
LRG_237:g.30210T>C
LRG_237p1:p.Cys791Arg
NC_000002.11:g.74594005A>G
NM_004082.4:c.2371T>C
NR_033935.2:n.2351T>C

Protein change:

C657R

Links:

dbSNP: rs1297844991

NCBI 1000 Genomes Browser:

rs1297844991

Molecular consequence:

NM_001135040.3:c.2311T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001135041.3:c.1969T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001190836.2:c.2260T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001190837.2:c.2350T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378991.1:c.2320T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001378992.1:c.2302T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004082.5:c.2371T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023019.4:c.1969T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_033935.2:n.2351T>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001221806	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 27, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001221806

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 27, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV001221806.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 791 of the DCTN1 protein (p.Cys791Arg). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 852663).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 30, 2024

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