rs8192697

chr12-21563055-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021957.4(GYS2):c.942-17G>A variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.256

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 261473.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-21563055-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYS2	NM_021957.4	c.942-17G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000261195.3
GYS2	XM_006719063.4	c.711-17G>A		splice_polypyrimidine_tract_variant, intron_variant
GYS2	XM_017019245.3	c.942-17G>A		splice_polypyrimidine_tract_variant, intron_variant
GYS2	XM_024448960.2	c.942-17G>A		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3	c.942-17G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_021957.4	P1

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

GnomAD3 exomes AF: 0.212 AC: 52905 AN: 250070 Hom.: 5854 AF XY: 0.212 AC XY: 28681 AN XY: 135410

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 SAS exome AF: 0.174

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

Gnomad4 AFR exome AF: 0.0765

Gnomad4 AMR exome AF: 0.194

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.277

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.212

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

Gnomad4 AFR AF: 0.0835

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.245

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.166

Alfa AF: 0.215 Hom.: 1009

Bravo AF: 0.180

Asia WGS AF: 0.184 AC: 637 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Glycogen storage disorder due to hepatic glycogen synthase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	12
Dann	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs8192697; hg19: chr12-21715989; COSMIC: COSV53923952;