12-21575411-T-C

Position:

• chr12-21575411-T-C

Variant summary

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

The NM_021957.4(GYS2):​c.495+455A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,008 control chromosomes in the GnomAD database, including 24,328 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 0.55 (24328 hom., cov: 31)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.55

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYS2	NM_021957.4	c.495+455A>G		intron_variant		ENST00000261195.3
GYS2	XM_006719063.4	c.264+455A>G		intron_variant
GYS2	XM_017019245.3	c.495+455A>G		intron_variant
GYS2	XM_024448960.2	c.495+455A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3	c.495+455A>G		intron_variant		1	NM_021957.4	P1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83927 AN: 151890 Hom.: 24318 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.552 AC: 83970 AN: 152008 Hom.: 24328 Cov.: 31 AF XY: 0.559 AC XY: 41501 AN XY: 74274

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.548

Alfa AF: 0.502 Hom.: 3080

Bravo AF: 0.553

Asia WGS AF: 0.724 AC: 2514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.014
DANN	Benign	0.52

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: rs10505873; hg19: chr12-21728345;