VCV000198031.21 - ClinVar

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

Germline

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.

(7)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Uncertain significance

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

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

Variation ID: 198031 Accession: VCV000198031.21

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.33 17: 50169207 (GRCh38) [ NCBI UCSC ] 17: 48246568 (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	Jun 29, 2015	Feb 4, 2024	Jul 20, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000023.4:c.700G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000014.1:p.Asp234Asn	missense
NM_000023.3:c.700G>A
NM_001135697.3:c.584+635G>A		intron variant
NR_135553.2:n.736G>A		non-coding transcript variant
NC_000017.11:g.50169207G>A
NC_000017.10:g.48246568G>A
NG_008889.1:g.8203G>A
LRG_203:g.8203G>A
LRG_203t1:c.700G>A

... more HGVS ... less HGVS

Protein change

D234N

Other names

Canonical SPDI

NC_000017.11:50169206:G:A

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) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00008

Exome Aggregation Consortium (ExAC) 0.00009

Links

ClinGen: CA246512 dbSNP: rs760608643 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.
SGCA		-	-	GRCh38 GRCh37	746	771

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	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Jun 22, 2023	RCV000723501.6
Autosomal recessive limb-girdle muscular dystrophy type 2D	Uncertain significance (5)	criteria provided, multiple submitters, no conflicts	Jul 20, 2023	RCV000648057.16

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.
Uncertain significance (Jun 13, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000231455.5 First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SGCA Number of individuals with the variant: 3 Sex: mixed
Uncertain significance (Jun 22, 2023)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000581760.5 First in ClinVar: Jun 29, 2015 Last updated: Jul 01, 2023	Comment: Observed in a patient with sarcoglycanopathy in published literature; however, no further clinical information is available (Alonso-Prez et al., 2020); In silico analysis supports that … (more) Observed in a patient with sarcoglycanopathy in published literature; however, no further clinical information is available (Alonso-Prez et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29802408, 32875335) (less)
Uncertain significance (Jul 11, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2D Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002785620.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Uncertain significance (Oct 20, 2022)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2D Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000769867.6 First in ClinVar: May 28, 2018 Last updated: Nov 11, 2023	Publications: PubMed (2) PubMed: 28492532‚ 32875335 Comment: 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 … (more) 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. (less)
Uncertain significance (Feb 08, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2D Affected status: unknown Allele origin: germline	Genome-Nilou Lab Accession: SCV003931690.1 First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023
Uncertain significance (Jul 20, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Autosomal recessive limb-girdle muscular dystrophy type 2D Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003827584.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024
Uncertain significance (Sep 16, 2020)	no assertion criteria provided Method: clinical testing	Limb-girdle muscular dystrophy type 2D Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001453384.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021

Comment:

Observed in a patient with sarcoglycanopathy in published literature; however, no further clinical information is available (Alonso-Prez et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29802408, 32875335)

Comment:

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.

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
New genotype-phenotype correlations in a large European cohort of patients with sarcoglycanopathy.	Alonso-Pérez J	Brain : a journal of neurology	2020	PMID: 32875335
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SGCA	-	-	-	-

Text-mined citations for rs760608643 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

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

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs760608643 ...