rs10770836

Positions:

• chr12-21563807-A-G
• chr12-21563807-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000261195.3(GYS2):​c.824-462T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,012 control chromosomes in the GnomAD database, including 40,561 homozygotes. 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: 𝑓 0.73 (40561 hom., cov: 31)
• Consequence: GYS2 ENST00000261195.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYS2	NM_021957.4	c.824-462T>C		intron_variant		ENST00000261195.3	NP_068776.2
GYS2	XM_006719063.4	c.593-462T>C		intron_variant			XP_006719126.1
GYS2	XM_017019245.3	c.824-462T>C		intron_variant			XP_016874734.1
GYS2	XM_024448960.2	c.824-462T>C		intron_variant			XP_024304728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYS2	ENST00000261195.3	c.824-462T>C		intron_variant		1	NM_021957.4	ENSP00000261195	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110631 AN: 151894 Hom.: 40526 Cov.: 31

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.728 AC: 110723 AN: 152012 Hom.: 40561 Cov.: 31 AF XY: 0.733 AC XY: 54472 AN XY: 74300

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.671

Alfa AF: 0.742 Hom.: 7107

Bravo AF: 0.719

Asia WGS AF: 0.752 AC: 2611 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.50

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: rs10770836; hg19: chr12-21716741;