NM_024301.5(FKRP):c.779_785del (p.Glu260fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 26, 2020
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:: RCV002007547.6

Allele description [Variation Report for NM_024301.5(FKRP):c.779_785del (p.Glu260fs)]

NM_024301.5(FKRP):c.779_785del (p.Glu260fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.779_785del (p.Glu260fs)

HGVS:

NC_000019.10:g.46756229_46756235del
NG_008898.2:g.15184_15190del
NM_001039885.3:c.779_785del
NM_024301.5:c.779_785delMANE SELECT
NP_001034974.1:p.Glu260fs
NP_077277.1:p.Glu260fs
LRG_761t1:c.779_785del
LRG_761:g.15184_15190del
LRG_761p1:p.Glu260fs
NC_000019.9:g.47259484_47259490del
NC_000019.9:g.47259486_47259492del

Protein change:

E260fs

Links:

dbSNP: rs2122623346

NCBI 1000 Genomes Browser:

rs2122623346

Molecular consequence:

NM_001039885.3:c.779_785del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024301.5:c.779_785del - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002231602	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 26, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 11592034, 14742276, 12707425, 12666124, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002231602

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 26, 2020)

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

Abnormalities in alpha-dystroglycan expression in MDC1C and LGMD2I muscular dystrophies.

Brown SC, Torelli S, Brockington M, Yuva Y, Jimenez C, Feng L, Anderson L, Ugo I, Kroger S, Bushby K, Voit T, Sewry C, Muntoni F.

Am J Pathol. 2004 Feb;164(2):727-37.

PubMed [citation]

PMID:: 14742276
PMCID:: PMC1602276

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002231602.3

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

Description

This variant has not been reported in the literature in individuals with FKRP-related conditions. 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.Ser385*) have been determined to be pathogenic (PMID: 11592034, 14742276, 12707425, 12666124). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change creates a premature translational stop signal (p.Glu260Alafs*15) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 236 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: Sep 29, 2024

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