rs1871136

Variant names:

• chr12-21559611-A-G
• rs1871136
• NM_021957.4:c.1229+40T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-21559611-A-G
• chr12-21559611-A-T

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.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:4
• Conservation: PhyloP100: -0.985
• Publications: 9 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

ENSG00000285854 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.1229+40T>C		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.1229+40T>C		intron	N/A	ENSP00000261195.2	P54840
	ENSG00000285854	ENST00000647960.1		n.*1231+40T>C		intron	N/A	ENSP00000497202.1	A0A3B3IS95
	GYS2	ENST00000863011.1		c.1343+40T>C		intron	N/A	ENSP00000533070.1

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

GnomAD2 exomes AF: 0.768 AC: 188577 AN: 245472 AF XY: 0.769

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 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

African (AFR) AF: 0.663 AC: 15408 AN: 23224

American (AMR) AF: 0.782 AC: 34140 AN: 43652

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 15580 AN: 22566

East Asian (EAS) AF: 0.785 AC: 29132 AN: 37098

South Asian (SAS) AF: 0.787 AC: 58476 AN: 74278

European-Finnish (FIN) AF: 0.804 AC: 42571 AN: 52966

Middle Eastern (MID) AF: 0.629 AC: 2893 AN: 4600

European-Non Finnish (NFE) AF: 0.766 AC: 454473 AN: 593238

Other (OTH) AF: 0.739 AC: 30691 AN: 41546

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

African (AFR) AF: 0.677 AC: 28118 AN: 41522

American (AMR) AF: 0.742 AC: 11348 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2389 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3897 AN: 5184

South Asian (SAS) AF: 0.795 AC: 3834 AN: 4822

European-Finnish (FIN) AF: 0.809 AC: 8576 AN: 10598

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53175 AN: 67982

Other (OTH) AF: 0.686 AC: 1448 AN: 2110

Alfa AF: 0.754 Hom.: 14372

Bravo AF: 0.736

Asia WGS AF: 0.755 AC: 2613 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	-0.91
CADD	Benign	0.88
DANN	Benign	0.68
PhyloP100		-0.98
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1871136;

hg19: chr12-21712545;