chr12-21552122-T-G

Variant names:

• chr12-21552122-T-G
• rs1871143
• NM_021957.4:c.1423-5652A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021957.4(GYS2):​c.1423-5652A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.713 in 152,042 control chromosomes in the GnomAD database, including 39,469 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 0.71 (39469 hom., cov: 31)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 2 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: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ENSG00000285854 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.786 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS2	NM_021957.4	MANE Select	c.1423-5652A>C		intron	N/A	NP_068776.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS2	ENST00000261195.3	TSL:1 MANE Select	c.1423-5652A>C		intron	N/A	ENSP00000261195.2
	ENSG00000285854	ENST00000647960.1		n.*1425-5652A>C		intron	N/A	ENSP00000497202.1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108341 AN: 151924 Hom.: 39443 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.713 AC: 108428 AN: 152042 Hom.: 39469 Cov.: 31 AF XY: 0.718 AC XY: 53339 AN XY: 74338

African (AFR) AF: 0.560 AC: 23208 AN: 41412

American (AMR) AF: 0.731 AC: 11179 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2325 AN: 3466

East Asian (EAS) AF: 0.749 AC: 3859 AN: 5150

South Asian (SAS) AF: 0.807 AC: 3895 AN: 4824

European-Finnish (FIN) AF: 0.812 AC: 8606 AN: 10594

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53192 AN: 67982

Other (OTH) AF: 0.667 AC: 1409 AN: 2114

Alfa AF: 0.737 Hom.: 6059

Bravo AF: 0.697

Asia WGS AF: 0.755 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.97
DANN	Benign	0.56
PhyloP100		-0.24
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: rs1871143; hg19: chr12-21705056;