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NM_024301.5(FKRP):c.1354del (p.Leu452fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 2, 2021
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:
RCV001890091.6

Allele description [Variation Report for NM_024301.5(FKRP):c.1354del (p.Leu452fs)]

NM_024301.5(FKRP):c.1354del (p.Leu452fs)

Gene:
FKRP:fukutin related protein [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
19q13.32
Genomic location:
Preferred name:
NM_024301.5(FKRP):c.1354del (p.Leu452fs)
HGVS:
  • NC_000019.10:g.46756804del
  • NG_008898.2:g.15759del
  • NM_001039885.3:c.1354del
  • NM_024301.5:c.1354delMANE SELECT
  • NP_001034974.1:p.Leu452fs
  • NP_077277.1:p.Leu452fs
  • LRG_761t1:c.1354del
  • LRG_761:g.15759del
  • LRG_761p1:p.Leu452fs
  • NC_000019.9:g.47260058del
  • NC_000019.9:g.47260061del
Protein change:
L452fs
Links:
dbSNP: rs2122635879
NCBI 1000 Genomes Browser:
rs2122635879
Molecular consequence:
  • NM_001039885.3:c.1354del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_024301.5:c.1354del - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002142910Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 2, 2021) 		germlineclinical testing

PubMed (2)
[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

Spectrum of brain changes in patients with congenital muscular dystrophy and FKRP gene mutations.

Mercuri E, Topaloglu H, Brockington M, Berardinelli A, Pichiecchio A, Santorelli F, Rutherford M, Talim B, Ricci E, Voit T, Muntoni F.

Arch Neurol. 2006 Feb;63(2):251-7.

PubMed [citation]
PMID:
16476814

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, SCV002142910.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the FKRP protein. Other variant(s) that disrupt this region (p.Gln460*) have been determined to be pathogenic (PMID: 16476814, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with FKRP-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu452Cysfs*38) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the FKRP protein.

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

Last Updated: Sep 29, 2024