VCV000392545.13 - ClinVar

NM_000231.3(SGCG):c.579-2A>G

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic/Likely pathogenic

5 out of 6 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000231.3(SGCG):c.579-2A>G

Variation ID: 392545 Accession: VCV000392545.13

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q12.12 13: 23320635 (GRCh38) [ NCBI UCSC ] 13: 23894774 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 19, 2017	Jun 29, 2025	Apr 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000231.3:c.579-2A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice acceptor
NM_001378244.1:c.633-2A>G		splice acceptor
NM_001378245.1:c.579-2A>G		splice acceptor
NM_001378246.1:c.579-2A>G		splice acceptor
NC_000013.11:g.23320635A>G
NC_000013.10:g.23894774A>G
NG_008759.1:g.144715A>G
LRG_207:g.144715A>G
LRG_207t1:c.579-2A>G

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000013.11:23320634:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00000

Exome Aggregation Consortium (ExAC) 0.00003

The Genome Aggregation Database (gnomAD), exomes 0.00001

Links

ClinGen: CA6909794 dbSNP: rs754415994 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
SGCG		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	569	681

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Pathogenic (1)	criteria provided, single submitter	Jul 10, 2017	RCV000441409.2
Autosomal recessive limb-girdle muscular dystrophy type 2C	Pathogenic/Likely pathogenic (5)	criteria provided, multiple submitters, no conflicts	Apr 29, 2024	RCV000673462.13

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jul 10, 2017) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000535827.3 First in ClinVar: Mar 08, 2017 Last updated: Dec 19, 2017	Comment: The c.579-2 A>G pathogenic variant in the SGCG gene destroys the canonical splice acceptor site in intron 6. It is predicted to cause abnormal gene … (more) The c.579-2 A>G pathogenic variant in the SGCG gene destroys the canonical splice acceptor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.579-2 A>G variant is not observed at significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the c.579-2 A>G variant has not been published to our knowledge, other splice site variants in the SGCG gene have been reported in the Human Gene Mutation Database in association with limb-girdle muscular dystrophy (Stenson et al., 2014). (less)

Pathogenic (Sep 07, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2C Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV004201039.1 First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023

Pathogenic (Feb 14, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2C Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV004238355.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024

Likely pathogenic (Apr 29, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2C Affected status: unknown Allele origin: germline	Fulgent Genetics, Fulgent Genetics Accession: SCV005632140.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025

Likely pathogenic (Mar 08, 2021) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2C Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002270979.4 First in ClinVar: Mar 28, 2022 Last updated: Feb 25, 2025	Publications: PubMed (2) PubMed: 16199547‚ 18285821 Comment: This sequence change affects an acceptor splice site in intron 6 of the SGCG gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more) This sequence change affects an acceptor splice site in intron 6 of the SGCG gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SGCG are known to be pathogenic (PMID: 18285821). This variant is present in population databases (rs754415994, ExAC 0.006%). This variant has not been reported in the literature in individuals with SGCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 392545). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)

Likely pathogenic (Mar 16, 2018) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2C Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000798666.2 First in ClinVar: Aug 05, 2018 Last updated: Jun 29, 2025	Comment: This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.

Comment:

The c.579-2 A>G pathogenic variant in the SGCG gene destroys the canonical splice acceptor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.579-2 A>G variant is not observed at significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the c.579-2 A>G variant has not been published to our knowledge, other splice site variants in the SGCG gene have been reported in the Human Gene Mutation Database in association with limb-girdle muscular dystrophy (Stenson et al., 2014).

Comment:

This sequence change affects an acceptor splice site in intron 6 of the SGCG gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SGCG are known to be pathogenic (PMID: 18285821). This variant is present in population databases (rs754415994, ExAC 0.006%). This variant has not been reported in the literature in individuals with SGCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 392545). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Revised spectrum of mutations in sarcoglycanopathies.	Trabelsi M	European journal of human genetics : EJHG	2008	PMID: 18285821
Splicing in action: assessing disease causing sequence changes.	Baralle D	Journal of medical genetics	2005	PMID: 16199547

Text-mined citations for rs754415994 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jun 29, 2025

ClinVar Genomic variation as it relates to human health

NM_000231.3(SGCG):c.579-2A>G

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs754415994 ...