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NM_000337.6(SGCD):c.848A>G (p.Gln283Arg) AND not specified

Germline classification:
Likely benign (2 submissions)
Last evaluated:
Jun 10, 2022
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:
RCV000036266.6

Allele description [Variation Report for NM_000337.6(SGCD):c.848A>G (p.Gln283Arg)]

NM_000337.6(SGCD):c.848A>G (p.Gln283Arg)

Gene:
SGCD:sarcoglycan delta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q33.3
Genomic location:
Preferred name:
NM_000337.6(SGCD):c.848A>G (p.Gln283Arg)
HGVS:
  • NC_000005.10:g.156759365A>G
  • NG_008693.2:g.894023A>G
  • NM_000337.6:c.848A>GMANE SELECT
  • NM_001128209.2:c.845A>G
  • NP_000328.2:p.Gln283Arg
  • NP_000328.2:p.Gln283Arg
  • NP_001121681.1:p.Gln282Arg
  • LRG_205t1:c.848A>G
  • LRG_205:g.894023A>G
  • LRG_205p1:p.Gln283Arg
  • NC_000005.9:g.156186376A>G
  • NM_000337.5:c.848A>G
  • NM_001128209.1:c.845A>G
  • c.848A>G
Protein change:
Q282R
Links:
dbSNP: rs397516338
NCBI 1000 Genomes Browser:
rs397516338
Molecular consequence:
  • NM_000337.6:c.848A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128209.2:c.845A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000059918Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Likely benign
(Nov 25, 2014) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002555818Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Jun 10, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided22not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

A Haplotype of Two Novel Polymorphisms in δ-Sarcoglycan Gene Increases Risk of Dilated Cardiomyopathy in Mongoloid Population.

Chen J, Jin Y, Wang H, Wei S, Chen D, Ying L, Zhou Q, Li G, Li J, Gao J, Kato N, Hu W, Li Y, Wang Y.

PLoS One. 2015;10(12):e0145602. doi: 10.1371/journal.pone.0145602.

PubMed [citation]
PMID:
26720722
PMCID:
PMC4697846

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059918.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

p.Gln283Arg in exon 9 of SGCD: This variant is not expected to have clinical sig nificance because it has been identified in 0.6% (57/8734) of East Asian chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs397516338).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002555818.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: SGCD c.848A>G (p.Gln283Arg) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00056 in 248152 control chromosomes (gnomAD), predominantly at a frequency of 0.0076 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 11 fold of the estimated maximal expected allele frequency for a pathogenic variant in SGCD causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive phenotype (0.00072), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.848A>G in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive has been reported. One publication has found that the variant protein interacts with other SGC proteins in an identical manner as wild-type, although there is reduced cell surface expression of the complete SGC complex (Chen_2015). Five ClinVar submitters have assessed the variant since 2014: all five classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 13, 2024