Variant rs73238708 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_021957.4(GYS2):c.1423-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0038 in 1,551,594 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 35 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 37 hom. )

Consequence

GYS2
NM_021957.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.572

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=-0.79).

BP6

Variant 12-21546491-T-C is Benign according to our data. Variant chr12-21546491-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261467.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1877/151414) while in subpopulation AFR AF= 0.037 (1525/41234). AF 95% confidence interval is 0.0354. There are 35 homozygotes in gnomad4. There are 880 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
GYS2	NM_021957.4 linkuse as main transcript	c.1423-21A>G	intron_variant	ENST00000261195.3	NP_068776.2
GYS2	XM_006719063.4 linkuse as main transcript	c.1192-21A>G	intron_variant		XP_006719126.1
GYS2	XM_024448960.2 linkuse as main transcript	c.1423-21A>G	intron_variant		XP_024304728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYS2	ENST00000261195.3 linkuse as main transcript	c.1423-21A>G		intron_variant		1	NM_021957.4	ENSP00000261195	P1

Frequencies

GnomAD3 genomes

AF:

0.0124

AC:

1873

AN:

151300

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0370

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00921

Gnomad ASJ

AF:

0.00752

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000624

Gnomad FIN

AF:

0.000289

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.00199

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00499

AC:

1030

AN:

206216

Hom.:

AF XY:

0.00418

AC XY:

465

AN XY:

111346

show subpopulations

Gnomad AFR exome

AF:

0.0407

Gnomad AMR exome

AF:

0.00676

Gnomad ASJ exome

AF:

0.00639

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000970

Gnomad FIN exome

AF:

0.000319

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00527

GnomAD4 exome

AF:

0.00288

AC:

4026

AN:

1400180

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

1982

AN XY:

696554

show subpopulations

Gnomad4 AFR exome

AF:

0.0391

Gnomad4 AMR exome

AF:

0.00704

Gnomad4 ASJ exome

AF:

0.00678

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.000606

Gnomad4 FIN exome

AF:

0.000255

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.00598

GnomAD4 genome

AF:

0.0124

AC:

1877

AN:

151414

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

880

AN XY:

73962

show subpopulations

Gnomad4 AFR

AF:

0.0370

Gnomad4 AMR

AF:

0.00920

Gnomad4 ASJ

AF:

0.00752

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000289

Gnomad4 NFE

AF:

0.00200

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.00701

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00520

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.86

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