VCV002020749.5 - ClinVar

NM_000294.3(PHKG2):c.334_337del (p.Lys112fs)

Germline

Classification

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

Pathogenic/Likely pathogenic
Pathogenic (1); Likely pathogenic (1)

2 out of 2 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_000294.3(PHKG2):c.334_337del (p.Lys112fs)

Variation ID: 2020749 Accession: VCV002020749.5

Type and length

Deletion, 4 bp

Location

Cytogenetic: 16p11.2 16: 30753237-30753240 (GRCh38) [ NCBI UCSC ] 16: 30764558-30764561 (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	Feb 8, 2023	Feb 23, 2026	Jun 17, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000294.3:c.334_337del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000285.1:p.Lys112fs	frameshift
NM_001172432.2:c.334_337del	NP_001165903.1:p.Lys112fs	frameshift
NC_000016.10:g.30753239_30753242del
NC_000016.9:g.30764560_30764563del
NG_016616.2:g.9941_9944del

... more HGVS ... less HGVS

Protein change

K112fs

Other names

Canonical SPDI

NC_000016.10:30753236:GGAAGG:GG

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.

Links

ClinGen: CA622170309 dbSNP: rs1567261757 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.
PHKG2		Gene associated with autosomal recessive phenotype	Not yet evaluated	GRCh38 GRCh37	434	532

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.
Glycogen storage disease IXc	Pathogenic/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Jun 17, 2024	RCV002857514.6

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.	Expand all rows Collapse all rows 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.
Likely pathogenic (Jun 17, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Glycogen storage disease IXc	Fulgent Genetics, Fulgent Genetics Accession: SCV005645749.1 First in ClinVar: Jan 25, 2025 Last updated: Jan 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Jul 30, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Glycogen storage disease IXc	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003226314.4 First in ClinVar: Feb 07, 2023 Last updated: Feb 23, 2026	Publications: PubMed (3) PubMed: 17689125‚ 21646031‚ 8896567 Comment: show This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Lys112Glufs*29) in the PHKG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHKG2 are known to be pathogenic (PMID: 8896567, 17689125, 21646031). This variant has not been reported in the literature in individuals affected with PHKG2-related conditions. For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Lys112Glufs*29) in the PHKG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHKG2 are known to be pathogenic (PMID: 8896567, 17689125, 21646031). This variant has not been reported in the literature in individuals affected with PHKG2-related conditions. For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Liver glycogen storage diseases due to phosphorylase system deficiencies: diagnosis thanks to non invasive blood enzymatic and molecular studies.	Davit-Spraul A	Molecular genetics and metabolism	2011	PMID: 21646031
Glycogen storage disease type IX: High variability in clinical phenotype.	Beauchamp NJ	Molecular genetics and metabolism	2007	PMID: 17689125
Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans.	Maichele AJ	Nature genetics	1996	PMID: 8896567

Text-mined citations for rs1567261757 ...

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 Apr 13, 2026