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NM_005518.4(HMGCS2):c.605G>A (p.Ser202Asn) AND 3-hydroxy-3-methylglutaryl-CoA synthase deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 28, 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:
RCV002838612.3

Allele description [Variation Report for NM_005518.4(HMGCS2):c.605G>A (p.Ser202Asn)]

NM_005518.4(HMGCS2):c.605G>A (p.Ser202Asn)

Gene:
HMGCS2:3-hydroxy-3-methylglutaryl-CoA synthase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p12
Genomic location:
Preferred name:
NM_005518.4(HMGCS2):c.605G>A (p.Ser202Asn)
HGVS:
  • NC_000001.11:g.119759944C>T
  • NG_013348.1:g.13989G>A
  • NM_001166107.1:c.560-662G>A
  • NM_005518.4:c.605G>AMANE SELECT
  • NP_005509.1:p.Ser202Asn
  • NP_005509.1:p.Ser202Asn
  • LRG_447t1:c.605G>A
  • LRG_447t2:c.560-662G>A
  • LRG_447:g.13989G>A
  • LRG_447p1:p.Ser202Asn
  • NC_000001.10:g.120302567C>T
  • NM_005518.3:c.605G>A
Protein change:
S202N
Molecular consequence:
  • NM_001166107.1:c.560-662G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_005518.4:c.605G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMGCS2D)
Synonyms:
HMGCS2 DEFICIENCY; MITOCHONDRIAL HMG-CoA SYNTHASE DEFICIENCY; mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011614; MedGen: C2751532; Orphanet: 35701; OMIM: 605911

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003218391Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 28, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003218391.2

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with HMGCS2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 202 of the HMGCS2 protein (p.Ser202Asn).

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

Last Updated: Sep 29, 2024