rs56029513

Variant names:

• chr16-30751565-C-G
• rs56029513
• NM_000294.3:c.288C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-30751565-C-G
• chr16-30751565-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_000294.3(PHKG2):​c.288C>G​(p.Ser96Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. S96S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHKG2 NM_000294.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.65
• Publications: 0 publications found

Genes affected

PHKG2 (HGNC:8931): (phosphorylase kinase catalytic subunit gamma 2) Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, and encoded by one gene. The gamma subunit also includes the skeletal muscle and hepatic isoforms, and the hepatic isoform is encoded by this gene. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9C, also known as autosomal liver glycogenosis. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

PHKG2 Gene-Disease associations (from GenCC):

• glycogen storage disease IXc

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• glycogen storage disease due to liver phosphorylase kinase deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000260899 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 16-30751565-C-G is Benign according to our data. Variant chr16-30751565-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2781849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.64 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000294.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	NM_000294.3	MANE Select	c.288C>G	p.Ser96Ser	synonymous	Exon 4 of 10	NP_000285.1
	PHKG2	NM_001172432.2		c.288C>G	p.Ser96Ser	synonymous	Exon 4 of 11	NP_001165903.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHKG2	ENST00000563588.6	TSL:1 MANE Select	c.288C>G	p.Ser96Ser	synonymous	Exon 4 of 10	ENSP00000455607.1
	PHKG2	ENST00000569762.1	TSL:1	n.532C>G		non_coding_transcript_exon	Exon 2 of 2
	PHKG2	ENST00000328273.11	TSL:5	c.288C>G	p.Ser96Ser	synonymous	Exon 4 of 10	ENSP00000329968.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Glycogen storage disease IXc (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-0.39
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56029513; hg19: chr16-30762886;