Variant 12-21539232-CAA-CA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_021957.4(GYS2):c.1890+25delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 36275 hom., cov: 0)

Exomes 𝑓: 0.76 ( 322768 hom. )

Consequence

GYS2
NM_021957.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00400

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 -16 ACMG points.

BP6

Variant 12-21539232-CA-C is Benign according to our data. Variant chr12-21539232-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 261469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-21539232-CA-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
GYS2	NM_021957.4 linkuse as main transcript	c.1890+25delT	intron_variant	ENST00000261195.3	NP_068776.2	P54840
GYS2	XM_024448960.2 linkuse as main transcript	c.1890+25delT	intron_variant		XP_024304728.1
GYS2	XM_006719063.4 linkuse as main transcript	c.1659+25delT	intron_variant		XP_006719126.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GYS2	ENST00000261195.3 linkuse as main transcript	c.1890+25delT	intron_variant		1	NM_021957.4	ENSP00000261195.2	P54840
ENSG00000285854	ENST00000647960.1 linkuse as main transcript	n.*1892+25delT	intron_variant				ENSP00000497202.1	A0A3B3IS95
SPX	ENST00000649016.1 linkuse as main transcript	n.2724delA	non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

102932

AN:

151478

Hom.:

36256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.479

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.730

Gnomad ASJ

AF:

0.663

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.779

Gnomad FIN

AF:

0.800

Gnomad MID

AF:

0.567

Gnomad NFE

AF:

0.760

Gnomad OTH

AF:

0.629

GnomAD3 exomes

AF:

0.752

AC:

183494

AN:

244042

Hom.:

69583

AF XY:

0.753

AC XY:

99276

AN XY:

131820

show subpopulations

Gnomad AFR exome

AF:

0.474

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.674

Gnomad EAS exome

AF:

0.785

Gnomad SAS exome

AF:

0.777

Gnomad FIN exome

AF:

0.800

Gnomad NFE exome

AF:

0.756

Gnomad OTH exome

AF:

0.722

GnomAD4 exome

AF:

0.757

AC:

848202

AN:

1120680

Hom.:

322768

Cov.:

AF XY:

0.757

AC XY:

433810

AN XY:

573138

show subpopulations

Gnomad4 AFR exome

AF:

0.465

Gnomad4 AMR exome

AF:

0.816

Gnomad4 ASJ exome

AF:

0.669

Gnomad4 EAS exome

AF:

0.814

Gnomad4 SAS exome

AF:

0.770

Gnomad4 FIN exome

AF:

0.793

Gnomad4 NFE exome

AF:

0.763

Gnomad4 OTH exome

AF:

0.719

GnomAD4 genome

AF:

0.679

AC:

103002

AN:

151596

Hom.:

36275

Cov.:

AF XY:

0.684

AC XY:

50691

AN XY:

74072

show subpopulations

Gnomad4 AFR

AF:

0.479

Gnomad4 AMR

AF:

0.731

Gnomad4 ASJ

AF:

0.663

Gnomad4 EAS

AF:

0.782

Gnomad4 SAS

AF:

0.778

Gnomad4 FIN

AF:

0.800

Gnomad4 NFE

AF:

0.760

Gnomad4 OTH

AF:

0.632

Bravo

AF:

0.664

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely 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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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