NM_024301.5(FKRP):c.722_791del (p.Ala241fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 30, 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:: RCV002857109.3

Allele description [Variation Report for NM_024301.5(FKRP):c.722_791del (p.Ala241fs)]

NM_024301.5(FKRP):c.722_791del (p.Ala241fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.722_791del (p.Ala241fs)

HGVS:

NC_000019.10:g.46756172_46756241del
NG_008898.2:g.15127_15196del
NM_001039885.3:c.722_791del
NM_024301.5:c.722_791delMANE SELECT
NP_001034974.1:p.Ala241fs
NP_077277.1:p.Ala241fs
LRG_761t1:c.722_791del
LRG_761:g.15127_15196del
LRG_761p1:p.Ala241fs
NC_000019.9:g.47259426_47259495del
NC_000019.9:g.47259429_47259498del

Protein change:

A241fs

Molecular consequence:

NM_001039885.3:c.722_791del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024301.5:c.722_791del - 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

Recent activity

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PH domain-containing protein [Radiobacillus deserti]
PH domain-containing protein [Radiobacillus deserti]
gi|1707798879|gnl|PRJNA554471|FN924 5|gb|QDP39144.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003222061	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003222061

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 30, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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, SCV003222061.2

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

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.Leu452Cysfs*38) have been determined to be pathogenic (Invitae). 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.Ala241Glyfs*13) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 255 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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