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NM_005198.5(CHKB):c.224+5G>C AND Megaconial type congenital muscular dystrophy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Aug 28, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001245358.8

Allele description [Variation Report for NM_005198.5(CHKB):c.224+5G>C]

NM_005198.5(CHKB):c.224+5G>C

Genes:
CHKB-CPT1B:CHKB-CPT1B readthrough (NMD candidate) [Gene - HGNC]
CHKB:choline kinase beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q13.33
Genomic location:
Preferred name:
NM_005198.5(CHKB):c.224+5G>C
HGVS:
  • NC_000022.11:g.50582553C>G
  • NG_012643.1:g.1115G>C
  • NG_029213.1:g.5447G>C
  • NM_005198.5:c.224+5G>CMANE SELECT
  • LRG_855t1:c.224+5G>C
  • LRG_855:g.5447G>C
  • NC_000022.10:g.51020982C>G
  • NM_005198.3:c.224+5G>C
  • NM_005198.4:c.224+5G>C
Links:
dbSNP: rs765251030
NCBI 1000 Genomes Browser:
rs765251030
Molecular consequence:
  • NM_005198.5:c.224+5G>C - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

Condition(s)

Name:
Megaconial type congenital muscular dystrophy (MDCMC)
Synonyms:
MUSCULAR DYSTROPHY, CONGENITAL, WITH MITOCHONDRIAL STRUCTURAL ABNORMALITIES; CHKB-Related Muscle Diseases
Identifiers:
MONDO: MONDO:0011246; MedGen: C1865233; Orphanet: 280671; OMIM: 602541

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001418641Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 28, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001432144Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Mar 6, 2018)
paternalclinical 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
African American,Causasianspaternalyes11not providednot providednot providedclinical testing

Citations

PubMed

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]
PMID:
9536098
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001418641.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change falls in intron 1 of the CHKB gene. It does not directly change the encoded amino acid sequence of the CHKB protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs765251030, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CHKB-related conditions. ClinVar contains an entry for this variant (Variation ID: 423804). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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 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.

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

From Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN, SCV001432144.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1African American,Causasians1not providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyesnot providedbloodnot provided1not provided1not provided

Last Updated: Sep 29, 2024