NM_024301.5(FKRP):c.961G>A (p.Ala321Thr) AND Walker-Warburg congenital muscular dystrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 5, 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:: RCV003067994.2

Allele description [Variation Report for NM_024301.5(FKRP):c.961G>A (p.Ala321Thr)]

NM_024301.5(FKRP):c.961G>A (p.Ala321Thr)

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.961G>A (p.Ala321Thr)

HGVS:

NC_000019.10:g.46756411G>A
NG_008898.2:g.15366G>A
NM_001039885.3:c.961G>A
NM_024301.5:c.961G>AMANE SELECT
NP_001034974.1:p.Ala321Thr
NP_077277.1:p.Ala321Thr
LRG_761t1:c.961G>A
LRG_761:g.15366G>A
LRG_761p1:p.Ala321Thr
NC_000019.9:g.47259668G>A

Protein change:

A321T

Molecular consequence:

NM_001039885.3:c.961G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_024301.5:c.961G>A - missense variant - [Sequence Ontology: SO:0001583]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003451620	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 33200426, 16143867, 31268217, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003451620

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 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

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

Limb girdle muscular dystrophy type 2I caused by a novel missense mutation in the FKRP gene presenting as acute virus-associated myositis in infancy.

von der Hagen M, Kaindl AM, Koehler K, Mitzscherling P, Häusler HJ, Stoltenburg-Didinger G, Huebner A.

Eur J Pediatr. 2006 Jan;165(1):62-3. Epub 2005 Sep 6. No abstract available.

PubMed [citation]

PMID:: 16143867

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003451620.1

#	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 replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 321 of the FKRP protein (p.Ala321Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 33200426). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ala321 amino acid residue in FKRP. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16143867, 31268217). This suggests that this residue is clinically significant, and that variants that disrupt this residue 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

ClinVar

Relating variation to medicine