NM_000023.4(SGCA):c.700G>A (p.Asp234Asn) AND Autosomal recessive limb-girdle muscular dystrophy type 2D

Germline classification:: Uncertain significance (5 submissions)
Last evaluated:: Jul 20, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000648057.15

Allele description [Variation Report for NM_000023.4(SGCA):c.700G>A (p.Asp234Asn)]

NM_000023.4(SGCA):c.700G>A (p.Asp234Asn)

Gene:

SGCA:sarcoglycan alpha [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.33

Genomic location:

Preferred name:

NM_000023.4(SGCA):c.700G>A (p.Asp234Asn)

HGVS:

NC_000017.11:g.50169207G>A
NG_008889.1:g.8203G>A
NM_000023.4:c.700G>AMANE SELECT
NM_001135697.3:c.584+635G>A
NP_000014.1:p.Asp234Asn
LRG_203t1:c.700G>A
LRG_203:g.8203G>A
NC_000017.10:g.48246568G>A
NM_000023.2:c.700G>A
NM_000023.3:c.700G>A
NR_135553.2:n.736G>A

Protein change:

D234N

Links:

dbSNP: rs760608643

NCBI 1000 Genomes Browser:

rs760608643

Molecular consequence:

NM_001135697.3:c.584+635G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000023.4:c.700G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_135553.2:n.736G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2D (LGMDR3)
Synonyms:: ADHALINOPATHY, PRIMARY; Limb-girdle muscular dystrophy, type 2D; Muscular dystrophy limb-girdle with alpha-sarcoglycan; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011968; MedGen: C2936332; Orphanet: 62; OMIM: 608099

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000769867	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 20, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32875335, 28492532
SCV001453384	Natera, Inc.	no assertion criteria provided	Uncertain significance (Sep 16, 2020)	germline	clinical testing
SCV002785620	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 11, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003827584	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003931690	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 8, 2023)	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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy.

Alonso-Pérez J, González-Quereda L, Bello L, Guglieri M, Straub V, Gallano P, Semplicini C, Pegoraro E, Zangaro V, Nascimento A, Ortez C, Comi GP, Dam LT, De Visser M, van der Kooi AJ, Garrido C, Santos M, Schara U, Gangfuß A, Løkken N, Storgaard JH, Vissing J, et al.

Brain. 2020 Sep 1;143(9):2696-2708. doi: 10.1093/brain/awaa228. Erratum in: Brain. 2023 Jan 5;146(1):e9. doi: 10.1093/brain/awac371.

PubMed [citation]

PMID:: 32875335

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

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000769867.6

#	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 replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 234 of the SGCA protein (p.Asp234Asn). This variant is present in population databases (rs760608643, gnomAD 0.06%). This missense change has been observed in individual(s) with clinical features of SGCA-related conditions (PMID: 32875335). ClinVar contains an entry for this variant (Variation ID: 198031). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SGCA protein function. 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

From Natera, Inc., SCV001453384.1

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

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002785620.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003827584.2

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

#	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

From Genome-Nilou Lab, SCV003931690.1

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

#	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 16, 2024

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