rs2306179

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-21568699-C-T
• chr12-21568699-C-A
• chr12-21568699-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021957.4(GYS2):​c.823+166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,064 control chromosomes in the GnomAD database, including 38,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (38320 hom., cov: 32)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Genomics England PanelApp

ENSG00000285854 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-21568699-C-T is Benign according to our data. Variant chr12-21568699-C-T is described in ClinVar as Benign. ClinVar VariationId is 1265728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021957.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS2	NM_021957.4	MANE Select	c.823+166G>A		intron	N/A	NP_068776.2	P54840

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS2	ENST00000261195.3	TSL:1 MANE Select	c.823+166G>A		intron	N/A	ENSP00000261195.2	P54840
	ENSG00000285854	ENST00000647960.1		n.*825+166G>A		intron	N/A	ENSP00000497202.1	A0A3B3IS95
	GYS2	ENST00000863011.1		c.937+166G>A		intron	N/A	ENSP00000533070.1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106963 AN: 151946 Hom.: 38287 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.704 AC: 107053 AN: 152064 Hom.: 38320 Cov.: 32 AF XY: 0.710 AC XY: 52757 AN XY: 74328

African (AFR) AF: 0.566 AC: 23459 AN: 41442

American (AMR) AF: 0.717 AC: 10958 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2376 AN: 3472

East Asian (EAS) AF: 0.751 AC: 3889 AN: 5178

South Asian (SAS) AF: 0.791 AC: 3805 AN: 4810

European-Finnish (FIN) AF: 0.803 AC: 8484 AN: 10562

Middle Eastern (MID) AF: 0.589 AC: 172 AN: 292

European-Non Finnish (NFE) AF: 0.762 AC: 51820 AN: 67994

Other (OTH) AF: 0.650 AC: 1374 AN: 2114

Alfa AF: 0.736 Hom.: 5188

Bravo AF: 0.690

Asia WGS AF: 0.746 AC: 2589 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.79
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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;