NM_024301.5(FKRP):c.979dup (p.Arg327fs) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 30, 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:: RCV001390523.7

Allele description [Variation Report for NM_024301.5(FKRP):c.979dup (p.Arg327fs)]

NM_024301.5(FKRP):c.979dup (p.Arg327fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

19q13.32

Genomic location:

Preferred name:

NM_024301.5(FKRP):c.979dup (p.Arg327fs)

HGVS:

NC_000019.10:g.46756429dup
NG_008898.2:g.15384dup
NM_001039885.3:c.979dup
NM_024301.5:c.979dupMANE SELECT
NP_001034974.1:p.Arg327fs
NP_077277.1:p.Arg327fs
LRG_761t1:c.979dup
LRG_761:g.15384dup
LRG_761p1:p.Arg327fs
NC_000019.9:g.47259683_47259684insC
NC_000019.9:g.47259686dup

Protein change:

R327fs

Links:

dbSNP: rs2122628653

NCBI 1000 Genomes Browser:

rs2122628653

Molecular consequence:

NM_001039885.3:c.979dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_024301.5:c.979dup - 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
SCV001592265	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 30, 2020)	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

SCV001592265

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 30, 2020)

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, SCV001592265.4

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

Description

This sequence change results in a premature translational stop signal in the FKRP gene (p.Arg327Profs*63). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 169 amino acids of the FKRP protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FKRP-related conditions. This variant disrupts the C-terminus of the FKRP protein. Other variant(s) that disrupt this region (p.Trp432*) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. 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: Sep 29, 2024

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