NM_024301.5(FKRP):c.142dup (p.Arg48fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 3, 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:: RCV002834801.2

Allele description [Variation Report for NM_024301.5(FKRP):c.142dup (p.Arg48fs)]

NM_024301.5(FKRP):c.142dup (p.Arg48fs)

Gene:

FKRP:fukutin related protein [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.142dup (p.Arg48fs)

HGVS:

NC_000019.10:g.46755592dup
NG_008898.2:g.14547dup
NM_001039885.3:c.142dup
NM_024301.5:c.142dupMANE SELECT
NP_001034974.1:p.Arg48fs
NP_077277.1:p.Arg48fs
LRG_761t1:c.142dup
LRG_761:g.14547dup
LRG_761p1:p.Arg48fs
NC_000019.9:g.47258844_47258845insC
NC_000019.9:g.47258849dup

Protein change:

R48fs

Molecular consequence:

NM_001039885.3:c.142dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024301.5:c.142dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Walker-Warburg congenital muscular dystrophy
Synonyms:: Muscular dystrophy-dystroglycanopathy, type A; Walker-Warburg syndrome
Identifiers:: MONDO: MONDO:0000171; MedGen: C0265221; Orphanet: 899; OMIM: PS236670

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5-hydroxytryptamine receptor 5A [Homo sapiens]
5-hydroxytryptamine receptor 5A [Homo sapiens]
gi|13236497|ref|NP_076917.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003218488	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 3, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11592034, 12666124, 12707425, 14742276, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003218488

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 3, 2022)

germline

clinical testing

PubMed (5)
[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

Mutations in the fukutin-related protein gene (FKRP) cause a form of congenital muscular dystrophy with secondary laminin alpha2 deficiency and abnormal glycosylation of alpha-dystroglycan.

Brockington M, Blake DJ, Prandini P, Brown SC, Torelli S, Benson MA, Ponting CP, Estournet B, Romero NB, Mercuri E, Voit T, Sewry CA, Guicheney P, Muntoni F.

Am J Hum Genet. 2001 Dec;69(6):1198-209. Epub 2001 Oct 8.

PubMed [citation]

PMID:: 11592034
PMCID:: PMC1235559

Phenotypic spectrum associated with mutations in the fukutin-related protein gene.

Mercuri E, Brockington M, Straub V, Quijano-Roy S, Yuva Y, Herrmann R, Brown SC, Torelli S, Dubowitz V, Blake DJ, Romero NB, Estournet B, Sewry CA, Guicheney P, Voit T, Muntoni F.

Ann Neurol. 2003 Apr;53(4):537-42.

PubMed [citation]

PMID:: 12666124

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV003218488.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the FKRP protein in which other variant(s) (p.Ser385*) have been determined to be pathogenic (PMID: 11592034, 12666124, 12707425, 14742276). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with FKRP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg48Profs*13) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 448 amino acid(s) of the FKRP protein.

#	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: Mar 30, 2024

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