rs1871136

chr12-21559611-A-Gchr12-21559611-A-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.1229+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 1,045,352 control chromosomes in the GnomAD database, including 304,838 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (42625 hom., cov: 33)
  • Exomes 𝑓: 0.77 (262213 hom.)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.985

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=-0.91).
• BP6: Variant 12-21559611-A-G is Benign according to our data. Variant chr12-21559611-A-G is described in ClinVar as [Benign]. Clinvar id is 261464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYS2	NM_021957.4	c.1229+40T>C		intron_variant		ENST00000261195.3
GYS2	XM_006719063.4	c.998+40T>C		intron_variant
GYS2	XM_024448960.2	c.1229+40T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3	c.1229+40T>C		intron_variant		1	NM_021957.4	P1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113447 AN: 152066 Hom.: 42588 Cov.: 33

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.797

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.684

GnomAD3 exomes AF: 0.768 AC: 188577 AN: 245472 Hom.: 72735 AF XY: 0.769 AC XY: 101917 AN XY: 132568

Gnomad AFR exome AF: 0.668

Gnomad AMR exome AF: 0.786

Gnomad ASJ exome AF: 0.689

Gnomad EAS exome AF: 0.748

Gnomad SAS exome AF: 0.792

Gnomad FIN exome AF: 0.806

Gnomad NFE exome AF: 0.776

Gnomad OTH exome AF: 0.732

GnomAD4 exome AF: 0.765 AC: 683364 AN: 893168 Hom.: 262213 Cov.: 12 AF XY: 0.766 AC XY: 358796 AN XY: 468236

Gnomad4 AFR exome AF: 0.663

Gnomad4 AMR exome AF: 0.782

Gnomad4 ASJ exome AF: 0.690

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.804

Gnomad4 NFE exome AF: 0.766

Gnomad4 OTH exome AF: 0.739

GnomAD4 genome AF: 0.746 AC: 113542 AN: 152184 Hom.: 42625 Cov.: 33 AF XY: 0.749 AC XY: 55739 AN XY: 74402

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.752

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.809

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.686

Alfa AF: 0.751 Hom.: 8070

Bravo AF: 0.736

Asia WGS AF: 0.755 AC: 2613 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Genome-Nilou Lab

Aug 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.88
Dann	Benign	0.68

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: rs1871136; hg19: chr12-21712545;