NM_000290.4(PGAM2):c.485G>C (p.Arg162Pro) AND Glycogen storage disease type X

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 25, 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:: RCV003134810.5

Allele description [Variation Report for NM_000290.4(PGAM2):c.485G>C (p.Arg162Pro)]

NM_000290.4(PGAM2):c.485G>C (p.Arg162Pro)

Genes:

LOC129998341:ATAC-STARR-seq lymphoblastoid active region 25924 [Gene]
DBNL:drebrin like [Gene - OMIM - HGNC]
PGAM2:phosphoglycerate mutase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000290.4(PGAM2):c.485G>C (p.Arg162Pro)

HGVS:

NC_000007.14:g.44064942C>G
NG_013016.1:g.5646G>C
NG_177787.1:g.139C>G
NM_000290.4:c.485G>CMANE SELECT
NM_001014436.3:c.*4026C>GMANE SELECT
NM_001122956.2:c.*4026C>G
NM_001284313.2:c.*4026C>G
NM_001284315.2:c.*4026C>G
NM_001362723.2:c.*4026C>G
NM_014063.7:c.*4026C>G
NP_000281.2:p.Arg162Pro
NC_000007.13:g.44104541C>G

Protein change:

R162P

Molecular consequence:

NM_001014436.3:c.*4026C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001122956.2:c.*4026C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001284313.2:c.*4026C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001284315.2:c.*4026C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001362723.2:c.*4026C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_014063.7:c.*4026C>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000290.4:c.485G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease type X (GSD10)
Synonyms:: GSD X; PHOSPHOGLYCERATE MUTASE, MUSCLE, DEFICIENCY OF; Dimauro disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009865; MedGen: C0268149; Orphanet: 97234; OMIM: 261670

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003814900	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 13, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004281054	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 25, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003814900

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 13, 2022)

germline

clinical testing

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

SCV004281054

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 25, 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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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 Revvity Omics, Revvity, SCV003814900.2

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004281054.1

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

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 162 of the PGAM2 protein (p.Arg162Pro). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PGAM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2434672). 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 PGAM2 protein function with a positive predictive value of 80%. 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

Last Updated: Sep 29, 2024

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