NM_005198.5(CHKB):c.216C>G (p.Tyr72Ter) AND Megaconial type congenital muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 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:: RCV001385174.7

Allele description [Variation Report for NM_005198.5(CHKB):c.216C>G (p.Tyr72Ter)]

NM_005198.5(CHKB):c.216C>G (p.Tyr72Ter)

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.216C>G (p.Tyr72Ter)

HGVS:

NC_000022.11:g.50582566G>C
NG_012643.1:g.1102C>G
NG_029213.1:g.5434C>G
NM_005198.5:c.216C>GMANE SELECT
NP_005189.2:p.Tyr72Ter
LRG_855:g.5434C>G
NC_000022.10:g.51020995G>C
NR_027928.2:n.434C>G

Protein change:

Y72*

Links:

dbSNP: rs80067609

NCBI 1000 Genomes Browser:

rs80067609

Molecular consequence:

NR_027928.2:n.434C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_005198.5:c.216C>G - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001584938	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21665002, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001584938

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

A congenital muscular dystrophy with mitochondrial structural abnormalities caused by defective de novo phosphatidylcholine biosynthesis.

Mitsuhashi S, Ohkuma A, Talim B, Karahashi M, Koumura T, Aoyama C, Kurihara M, Quinlivan R, Sewry C, Mitsuhashi H, Goto K, Koksal B, Kale G, Ikeda K, Taguchi R, Noguchi S, Hayashi YK, Nonaka I, Sher RB, Sugimoto H, Nakagawa Y, Cox GA, et al.

Am J Hum Genet. 2011 Jun 10;88(6):845-851. doi: 10.1016/j.ajhg.2011.05.010.

PubMed [citation]

PMID:: 21665002
PMCID:: PMC3113344

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, SCV001584938.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1072448). This variant has not been reported in the literature in individuals affected with CHKB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr72*) in the CHKB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHKB are known to be pathogenic (PMID: 21665002).

#	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: Sep 29, 2024

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