NM_024301.5(FKRP):c.949del (p.Cys317fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 4, 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:: RCV002604120.3

Allele description [Variation Report for NM_024301.5(FKRP):c.949del (p.Cys317fs)]

NM_024301.5(FKRP):c.949del (p.Cys317fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.949del (p.Cys317fs)

HGVS:

NC_000019.10:g.46756399del
NG_008898.2:g.15354del
NM_001039885.3:c.949del
NM_024301.5:c.949delMANE SELECT
NP_001034974.1:p.Cys317fs
NP_077277.1:p.Cys317fs
LRG_761t1:c.949del
LRG_761:g.15354del
LRG_761p1:p.Cys317fs
NC_000019.9:g.47259656del

Protein change:

C317fs

Molecular consequence:

NM_001039885.3:c.949del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024301.5:c.949del - 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
SCV002952155	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 4, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16476814, 18639457, 19299310, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002952155

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 4, 2022)

germline

clinical testing

PubMed (4)
[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

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

Cardiac assessment of limb-girdle muscular dystrophy 2I patients: an echography, Holter ECG and magnetic resonance imaging study.

Wahbi K, Meune C, Hamouda el H, Stojkovic T, Laforêt P, Bécane HM, Eymard B, Duboc D.

Neuromuscul Disord. 2008 Aug;18(8):650-5. doi: 10.1016/j.nmd.2008.06.365. Epub 2008 Jul 17.

PubMed [citation]

PMID:: 18639457

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002952155.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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.Ile478Thr) have been determined to be pathogenic (PMID: 16476814, 18639457, 19299310). 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.Cys317Alafs*111) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 179 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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