12-21546982-G-A

Position:

• chr12-21546982-G-A

Variant summary

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

The NM_021957.4(GYS2):​c.1423-512C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,954 control chromosomes in the GnomAD database, including 37,844 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 0.69 (37844 hom., cov: 31)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.301

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=-1.0).
• 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.1423-512C>T		intron_variant		ENST00000261195.3
GYS2	XM_006719063.4	c.1192-512C>T		intron_variant
GYS2	XM_024448960.2	c.1423-512C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3	c.1423-512C>T		intron_variant		1	NM_021957.4	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104886 AN: 151836 Hom.: 37824 Cov.: 31

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.650

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

GnomAD4 genome AF: 0.691 AC: 104960 AN: 151954 Hom.: 37844 Cov.: 31 AF XY: 0.696 AC XY: 51704 AN XY: 74284

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.796

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.652

Alfa AF: 0.737 Hom.: 6937

Bravo AF: 0.675

Asia WGS AF: 0.755 AC: 2621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.30

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: rs6487236; hg19: chr12-21699916;