12-21568699-C-A

Variant names:

• chr12-21568699-C-A
• rs2306179
• NM_021957.4:c.823+166G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021957.4(GYS2):​c.823+166G>T variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 3 publications found

Genes affected

GYS2 (HGNC:4707): (glycogen synthase 2) The protein encoded by this gene, liver glycogen synthase, catalyzes the rate-limiting step in the synthesis of glycogen - the transfer of a glucose molecule from UDP-glucose to a terminal branch of the glycogen molecule. Mutations in this gene cause glycogen storage disease type 0 (GSD-0) - a rare type of early childhood fasting hypoglycemia with decreased liver glycogen content. [provided by RefSeq, Dec 2009]

GYS2 Gene-Disease associations (from GenCC):

• glycogen storage disorder due to hepatic glycogen synthase deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ENSG00000285854 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYS2	NM_021957.4	c.823+166G>T		intron_variant	Intron 5 of 15	ENST00000261195.3	NP_068776.2
GYS2	XM_024448960.2	c.823+166G>T		intron_variant	Intron 5 of 16		XP_024304728.1
GYS2	XM_006719063.4	c.592+166G>T		intron_variant	Intron 4 of 14		XP_006719126.1
GYS2	XM_017019245.3	c.823+166G>T		intron_variant	Intron 5 of 8		XP_016874734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYS2	ENST00000261195.3	c.823+166G>T		intron_variant	Intron 5 of 15	1	NM_021957.4	ENSP00000261195.2
ENSG00000285854	ENST00000647960.1	n.*825+166G>T		intron_variant	Intron 12 of 22			ENSP00000497202.1
ENSG00000285854	ENST00000648372.1	n.750+166G>T		intron_variant	Intron 5 of 10

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.76
PhyloP100		0.16

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: rs2306179; hg19: chr12-21721633;