rs4639981

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_021957.4(GYS2):c.1169+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 1,354,606 control chromosomes in the GnomAD database, including 438,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 45053 hom., cov: 32)

Exomes 𝑓: 0.81 ( 393434 hom. )

Consequence

GYS2
NM_021957.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.657

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:

ENSG00000285854 (HGNC:):

ENSG00000285854 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=-0.89).

BP6

Variant 12-21560374-T-A is Benign according to our data. Variant chr12-21560374-T-A is described in ClinVar as [Benign]. Clinvar id is 261463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-21560374-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GYS2	NM_021957.4 link	c.1169+12A>T	intron_variant	Intron 8 of 15	ENST00000261195.3	NP_068776.2	P54840
GYS2	XM_024448960.2 link	c.1169+12A>T	intron_variant	Intron 8 of 16		XP_024304728.1
GYS2	XM_006719063.4 link	c.938+12A>T	intron_variant	Intron 7 of 14		XP_006719126.1
GYS2	XM_017019245.3 link	c.1169+12A>T	intron_variant	Intron 8 of 8		XP_016874734.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GYS2	ENST00000261195.3 link	c.1169+12A>T	intron_variant	Intron 8 of 15	1	NM_021957.4	ENSP00000261195.2	P54840
ENSG00000285854	ENST00000647960.1 link	n.*1171+12A>T	intron_variant	Intron 15 of 22			ENSP00000497202.1	A0A3B3IS95
ENSG00000285854	ENST00000648372.1 link	n.1096+12A>T	intron_variant	Intron 8 of 10

Frequencies

GnomAD3 genomes

AF:

0.767

AC:

116592

AN:

152016

Hom.:

45019

Cov.:

show subpopulations

Gnomad AFR

AF:

0.683

Gnomad AMI

AF:

0.799

Gnomad AMR

AF:

0.763

Gnomad ASJ

AF:

0.738

Gnomad EAS

AF:

0.752

Gnomad SAS

AF:

0.806

Gnomad FIN

AF:

0.824

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.812

Gnomad OTH

AF:

0.714

GnomAD3 exomes

AF:

0.791

AC:

198817

AN:

251222

Hom.:

79037

AF XY:

0.792

AC XY:

107564

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.676

Gnomad AMR exome

AF:

0.806

Gnomad ASJ exome

AF:

0.738

Gnomad EAS exome

AF:

0.749

Gnomad SAS exome

AF:

0.804

Gnomad FIN exome

AF:

0.822

Gnomad NFE exome

AF:

0.807

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

AF:

0.807

AC:

970991

AN:

1202472

Hom.:

393434

Cov.:

AF XY:

0.807

AC XY:

493451

AN XY:

611492

show subpopulations

Gnomad4 AFR exome

AF:

0.681

Gnomad4 AMR exome

AF:

0.802

Gnomad4 ASJ exome

AF:

0.744

Gnomad4 EAS exome

AF:

0.785

Gnomad4 SAS exome

AF:

0.803

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.817

Gnomad4 OTH exome

AF:

0.779

GnomAD4 genome

AF:

0.767

AC:

116683

AN:

152134

Hom.:

45053

Cov.:

AF XY:

0.770

AC XY:

57245

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.683

Gnomad4 AMR

AF:

0.764

Gnomad4 ASJ

AF:

0.738

Gnomad4 EAS

AF:

0.752

Gnomad4 SAS

AF:

0.805

Gnomad4 FIN

AF:

0.824

Gnomad4 NFE

AF:

0.812

Gnomad4 OTH

AF:

0.715

Alfa

AF:

0.780

Hom.:

8575

Bravo

AF:

0.757

Asia WGS

AF:

0.759

AC:

2632

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Glycogen storage disorder due to hepatic glycogen synthase deficiency

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 23, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.8

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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