Variant 12-21559611-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.985

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
GYS2	NM_021957.4 linkuse as main transcript	c.1229+40T>C	intron_variant	ENST00000261195.3
GYS2	XM_006719063.4 linkuse as main transcript	c.998+40T>C	intron_variant
GYS2	XM_024448960.2 linkuse as main transcript	c.1229+40T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3 linkuse as main transcript	c.1229+40T>C		intron_variant		1	NM_021957.4	P1

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

113447

AN:

152066

Hom.:

42588

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.768

AC:

188577

AN:

245472

Hom.:

72735

AF XY:

0.769

AC XY:

101917

AN XY:

132568

show subpopulations

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 SAS exome

AF:

0.792

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.:

AF XY:

0.766

AC XY:

358796

AN XY:

468236

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.782

Gnomad4 ASJ exome

AF:

0.690

Gnomad4 EAS exome

AF:

0.785

Gnomad4 SAS exome

AF:

0.787

Gnomad4 FIN exome

AF:

0.804

Gnomad4 NFE exome

AF:

0.766

Gnomad4 OTH exome

AF:

0.739

GnomAD4 genome

AF:

0.746

AC:

113542

AN:

152184

Hom.:

42625

Cov.:

AF XY:

0.749

AC XY:

55739

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.677

Gnomad4 AMR

AF:

0.742

Gnomad4 ASJ

AF:

0.688

Gnomad4 EAS

AF:

0.752

Gnomad4 SAS

AF:

0.795

Gnomad4 FIN

AF:

0.809

Gnomad4 NFE

AF:

0.782

Gnomad4 OTH

AF:

0.686

Alfa

AF:

0.751

Hom.:

8070

Bravo

AF:

0.736

Asia WGS

AF:

0.755

AC:

2613

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Glycogen storage disorder due to hepatic glycogen synthase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.88

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over