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NM_025233.7(COASY):c.1388-2A>G AND Neurodegeneration with brain iron accumulation 6

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 20, 2024
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:
RCV002937500.3

Allele description [Variation Report for NM_025233.7(COASY):c.1388-2A>G]

NM_025233.7(COASY):c.1388-2A>G

Gene:
COASY:Coenzyme A synthase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.2
Genomic location:
Preferred name:
NM_025233.7(COASY):c.1388-2A>G
HGVS:
  • NC_000017.11:g.42565469A>G
  • NG_029442.1:g.3410A>G
  • NG_034110.1:g.8396A>G
  • NG_136593.1:g.218A>G
  • NM_001042529.3:c.1388-2A>G
  • NM_001042532.4:c.1475-2A>G
  • NM_025233.6:c.1388-2A>G
  • NM_025233.7:c.1388-2A>GMANE SELECT
  • NC_000017.10:g.40717487A>G
  • NM_025233.7:c.1388-2A>G
Molecular consequence:
  • NM_001042529.3:c.1388-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001042532.4:c.1475-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_025233.7:c.1388-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Neurodegeneration with brain iron accumulation 6 (NBIA6)
Synonyms:
COASY protein-associated neurodegeneration
Identifiers:
MONDO: MONDO:0014290; MedGen: C4517377; Orphanet: 397725; OMIM: 615643

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003259446Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jan 20, 2024) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

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

Exome sequence reveals mutations in CoA synthase as a cause of neurodegeneration with brain iron accumulation.

Dusi S, Valletta L, Haack TB, Tsuchiya Y, Venco P, Pasqualato S, Goffrini P, Tigano M, Demchenko N, Wieland T, Schwarzmayr T, Strom TM, Invernizzi F, Garavaglia B, Gregory A, Sanford L, Hamada J, Bettencourt C, Houlden H, Chiapparini L, Zorzi G, Kurian MA, et al.

Am J Hum Genet. 2014 Jan 2;94(1):11-22. doi: 10.1016/j.ajhg.2013.11.008. Epub 2013 Dec 19.

PubMed [citation]
PMID:
24360804
PMCID:
PMC3882905
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003259446.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 6 of the COASY 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), and loss-of-function variants in COASY are known to be pathogenic (PMID: 24360804, 30089828). This variant is present in population databases (rs145108650, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with COASY-related conditions. ClinVar contains an entry for this variant (Variation ID: 2050208). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Nov 24, 2024