Variant chr12-21558177-G-C 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.1422+23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,321,506 control chromosomes in the GnomAD database, including 398,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.72 ( 40451 hom., cov: 31)

Exomes 𝑓: 0.78 ( 357993 hom. )

Consequence

GYS2
NM_021957.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.56

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=-0.96).

BP6

Variant 12-21558177-G-C is Benign according to our data. Variant chr12-21558177-G-C is described in ClinVar as [Benign]. Clinvar id is 261466.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.1422+23C>G	intron_variant	ENST00000261195.3
GYS2	XM_006719063.4 linkuse as main transcript	c.1191+23C>G	intron_variant
GYS2	XM_024448960.2 linkuse as main transcript	c.1422+23C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3 linkuse as main transcript	c.1422+23C>G		intron_variant		1	NM_021957.4	P1

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110049

AN:

151870

Hom.:

40414

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.633

Gnomad AMR

AF:

0.733

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.751

Gnomad SAS

AF:

0.797

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.604

Gnomad NFE

AF:

0.782

Gnomad OTH

AF:

0.667

GnomAD3 exomes

AF:

0.765

AC:

191420

AN:

250296

Hom.:

73661

AF XY:

0.767

AC XY:

103717

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.595

Gnomad AMR exome

AF:

0.785

Gnomad ASJ exome

AF:

0.690

Gnomad EAS exome

AF:

0.750

Gnomad SAS exome

AF:

0.793

Gnomad FIN exome

AF:

0.807

Gnomad NFE exome

AF:

0.778

Gnomad OTH exome

AF:

0.731

GnomAD4 exome

AF:

0.781

AC:

913207

AN:

1169518

Hom.:

357993

Cov.:

AF XY:

0.781

AC XY:

465427

AN XY:

595964

show subpopulations

Gnomad4 AFR exome

AF:

0.594

Gnomad4 AMR exome

AF:

0.780

Gnomad4 ASJ exome

AF:

0.693

Gnomad4 EAS exome

AF:

0.786

Gnomad4 SAS exome

AF:

0.792

Gnomad4 FIN exome

AF:

0.804

Gnomad4 NFE exome

AF:

0.790

Gnomad4 OTH exome

AF:

0.748

GnomAD4 genome

AF:

0.725

AC:

110142

AN:

151988

Hom.:

40451

Cov.:

AF XY:

0.729

AC XY:

54130

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.602

Gnomad4 AMR

AF:

0.733

Gnomad4 ASJ

AF:

0.689

Gnomad4 EAS

AF:

0.751

Gnomad4 SAS

AF:

0.795

Gnomad4 FIN

AF:

0.810

Gnomad4 NFE

AF:

0.782

Gnomad4 OTH

AF:

0.669

Alfa

AF:

0.696

Hom.:

3926

Bravo

AF:

0.711

Asia WGS

AF:

0.751

AC:

2606

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Oct 23, 2015	- -
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

-0.96

CADD

Benign

0.61

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

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