12-21568699-C-T

Position:

• chr12-21568699-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021957.4(GYS2):​c.823+166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,064 control chromosomes in the GnomAD database, including 38,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.70 (38320 hom., cov: 32)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.162

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-21568699-C-T is Benign according to our data. Variant chr12-21568699-C-T is described in ClinVar as [Benign]. Clinvar id is 1265728.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYS2	NM_021957.4	c.823+166G>A		intron_variant		ENST00000261195.3
GYS2	XM_006719063.4	c.592+166G>A		intron_variant
GYS2	XM_017019245.3	c.823+166G>A		intron_variant
GYS2	XM_024448960.2	c.823+166G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3	c.823+166G>A		intron_variant		1	NM_021957.4	P1

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106963 AN: 151946 Hom.: 38287 Cov.: 32

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.704 AC: 107053 AN: 152064 Hom.: 38320 Cov.: 32 AF XY: 0.710 AC XY: 52757 AN XY: 74328

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.751

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.803

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.650

Alfa AF: 0.736 Hom.: 5188

Bravo AF: 0.690

Asia WGS AF: 0.746 AC: 2589 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.79

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: rs2306179; hg19: chr12-21721633;