Variant 12-21536516-T-TA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_021957.4(GYS2):c.*437_*438insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0235 in 190,982 control chromosomes in the GnomAD database, including 187 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.028 ( 187 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 0 hom. )

Consequence

GYS2
NM_021957.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.412

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:

LOC124902896 (HGNC:):

LOC124902896 links:

SPX (HGNC:28139): (spexin hormone) The protein encoded by this gene is a hormone involved in modulation of cardiovascular and renal function. It has also been shown in rats to cause weight loss. Several transcript variants have been found for this gene. [provided by RefSeq, Feb 2016]

SPX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-21536516-T-TA is Benign according to our data. Variant chr12-21536516-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 307981.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GYS2	NM_021957.4 linkuse as main transcript	c.437_438insT	3_prime_UTR_variant	16/16	ENST00000261195.3
LOC124902896	XR_007063240.1 linkuse as main transcript	n.519-524dup	intron_variant, non_coding_transcript_variant
GYS2	XM_006719063.4 linkuse as main transcript	c.437_438insT	3_prime_UTR_variant	15/15
GYS2	XM_024448960.2 linkuse as main transcript	c.42+395_42+396insT	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
GYS2	ENST00000261195.3 linkuse as main transcript	c.437_438insT	3_prime_UTR_variant	16/16	1	NM_021957.4	P1
SPX	ENST00000537527.1 linkuse as main transcript	n.472-524dup	intron_variant, non_coding_transcript_variant		3
SPX	ENST00000649016.1 linkuse as main transcript	n.529-524dup	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0284

AC:

4315

AN:

152034

Hom.:

186

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0911

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.0104

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.0311

GnomAD4 exome

AF:

0.00412

AC:

160

AN:

38830

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

AN XY:

19812

show subpopulations

Gnomad4 AFR exome

AF:

0.0625

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.00409

Gnomad4 EAS exome

AF:

0.0110

Gnomad4 SAS exome

AF:

0.00157

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00172

Gnomad4 OTH exome

AF:

0.00643

GnomAD4 genome

AF:

0.0284

AC:

4326

AN:

152152

Hom.:

187

Cov.:

AF XY:

0.0276

AC XY:

2054

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0911

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.0104

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.00216

Gnomad4 OTH

AF:

0.0308

Bravo

AF:

0.0317

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Glycogen storage disorder due to hepatic glycogen synthase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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