rs8192697

Variant names:

• chr12-21563055-C-T
• rs8192697
• NM_021957.4:c.942-17G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-21563055-C-T
• chr12-21563055-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021957.4(GYS2):​c.942-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,582,930 control chromosomes in the GnomAD database, including 41,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3072 hom., cov: 32)
  • Exomes 𝑓: 0.23 (38753 hom.)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.256
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 12-21563055-C-T is Benign according to our data. Variant chr12-21563055-C-T is described in ClinVar as Benign. ClinVar VariationId is 261473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 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.942-17G>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.942-17G>A		intron	N/A	ENSP00000261195.2	P54840
	ENSG00000285854	ENST00000647960.1		n.*944-17G>A		intron	N/A	ENSP00000497202.1	A0A3B3IS95
	GYS2	ENST00000863011.1		c.1056-17G>A		intron	N/A	ENSP00000533070.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28455 AN: 151940 Hom.: 3071 Cov.: 32

Gnomad AFR AF: 0.0836

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.212 AC: 52905 AN: 250070 AF XY: 0.212

Gnomad AFR exome AF: 0.0808

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.266

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.232

Gnomad OTH exome AF: 0.205

GnomAD4 exome AF: 0.229 AC: 328057 AN: 1430872 Hom.: 38753 Cov.: 29 AF XY: 0.228 AC XY: 162868 AN XY: 713726

African (AFR) AF: 0.0765 AC: 2516 AN: 32902

American (AMR) AF: 0.194 AC: 8656 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 5070 AN: 25950

East Asian (EAS) AF: 0.277 AC: 10903 AN: 39432

South Asian (SAS) AF: 0.175 AC: 15012 AN: 85692

European-Finnish (FIN) AF: 0.239 AC: 12641 AN: 52892

Middle Eastern (MID) AF: 0.124 AC: 706 AN: 5710

European-Non Finnish (NFE) AF: 0.240 AC: 259933 AN: 1084208

Other (OTH) AF: 0.212 AC: 12620 AN: 59422

GnomAD4 genome AF: 0.187 AC: 28473 AN: 152058 Hom.: 3072 Cov.: 32 AF XY: 0.188 AC XY: 13956 AN XY: 74322

African (AFR) AF: 0.0835 AC: 3466 AN: 41514

American (AMR) AF: 0.189 AC: 2892 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1419 AN: 5174

South Asian (SAS) AF: 0.177 AC: 854 AN: 4822

European-Finnish (FIN) AF: 0.245 AC: 2583 AN: 10538

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16049 AN: 67948

Other (OTH) AF: 0.166 AC: 351 AN: 2114

Alfa AF: 0.215 Hom.: 1525

Bravo AF: 0.180

Asia WGS AF: 0.184 AC: 637 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Glycogen storage disorder due to hepatic glycogen synthase deficiency (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		-0.26
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: rs8192697; hg19: chr12-21715989; COSMIC: COSV53923952;