NM_024301.5(FKRP):c.1296G>A (p.Trp432Ter) AND Walker-Warburg congenital muscular dystrophy

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 3, 2023
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:: RCV000810942.6

Allele description

NM_024301.5(FKRP):c.1296G>A (p.Trp432Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.1296G>A (p.Trp432Ter)

HGVS:

NC_000019.10:g.46756746G>A
NG_008898.2:g.15701G>A
NM_001039885.3:c.1296G>A
NM_024301.5:c.1296G>AMANE SELECT
NP_001034974.1:p.Trp432Ter
NP_077277.1:p.Trp432Ter
LRG_761t1:c.1296G>A
LRG_761:g.15701G>A
LRG_761p1:p.Trp432Ter
NC_000019.9:g.47260003G>A
NM_024301.4:c.1296G>A

Protein change:

W432*

Links:

dbSNP: rs1599939853

NCBI 1000 Genomes Browser:

rs1599939853

Molecular consequence:

NM_001039885.3:c.1296G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_024301.5:c.1296G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000951184	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 3, 2023)	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

SCV000951184

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 3, 2023)

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 Invitae, SCV000951184.4

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

Description

This sequence change creates a premature translational stop signal (p.Trp432*) in the FKRP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 64 amino acid(s) of the FKRP protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FKRP-related conditions. ClinVar contains an entry for this variant (Variation ID: 654883). 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. For these reasons, this variant has been classified as Pathogenic.

#	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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