NM_024301.5(FKRP):c.1444dup (p.Gln482fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 13, 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:: RCV003008332.2

Allele description [Variation Report for NM_024301.5(FKRP):c.1444dup (p.Gln482fs)]

NM_024301.5(FKRP):c.1444dup (p.Gln482fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.1444dup (p.Gln482fs)

HGVS:

NC_000019.10:g.46756894dup
NG_008898.2:g.15849dup
NM_001039885.3:c.1444dup
NM_024301.5:c.1444dupMANE SELECT
NP_001034974.1:p.Gln482fs
NP_077277.1:p.Gln482fs
LRG_761t1:c.1444dup
LRG_761:g.15849dup
LRG_761p1:p.Gln482fs
NC_000019.9:g.47260146_47260147insC
NC_000019.9:g.47260151dup

Protein change:

Q482fs

Molecular consequence:

NM_001039885.3:c.1444dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024301.5:c.1444dup - 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
SCV003311267	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33200426, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003311267

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 13, 2022)

germline

clinical testing

PubMed (2)
[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

Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients.

Song D, Dai Y, Chen X, Fu X, Chang X, Wang N, Zhang C, Yan C, Zheng H, Wu L, Jiang L, Hua Y, Yang H, Wang Z, Dai T, Zhu W, Han C, Yuan Y, Kobayashi K, Toda T, Xiong H.

Clin Genet. 2021 Mar;99(3):384-395. doi: 10.1111/cge.13886. Epub 2021 Jan 19.

PubMed [citation]

PMID:: 33200426

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, SCV003311267.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change results in a frameshift in the FKRP gene (p.Gln482Profs*18). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acid(s) of the FKRP protein and extend the protein by 3 additional amino acid residues. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the FKRP protein in which other variant(s) (p.Tyr483Cys) have been observed in individuals with FKRP-related conditions (PMID: 33200426). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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