12-21539232-CAA-CA

Variant names:

• chr12-21539232-CA-C
• rs36023861
• NM_021957.4:c.1890+25delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.00400
• Publications: 2 publications found

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]

ENSG00000285854 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 261469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021957.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS2	NM_021957.4	MANE Select	c.1890+25delT		intron	N/A	NP_068776.2	P54840

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYS2	ENST00000261195.3	TSL:1 MANE Select	c.1890+25delT		intron	N/A	ENSP00000261195.2	P54840
	ENSG00000285854	ENST00000647960.1		n.*1892+25delT		intron	N/A	ENSP00000497202.1	A0A3B3IS95
	GYS2	ENST00000863011.1		c.2004+25delT		intron	N/A	ENSP00000533070.1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 102932 AN: 151478 Hom.: 36256 Cov.: 0

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

GnomAD2 exomes AF: 0.752 AC: 183494 AN: 244042 AF XY: 0.753

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 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.: 0 AF XY: 0.757 AC XY: 433810 AN XY: 573138

African (AFR) AF: 0.465 AC: 12420 AN: 26690

American (AMR) AF: 0.816 AC: 35284 AN: 43230

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 15945 AN: 23840

East Asian (EAS) AF: 0.814 AC: 30935 AN: 38026

South Asian (SAS) AF: 0.770 AC: 59609 AN: 77366

European-Finnish (FIN) AF: 0.793 AC: 41876 AN: 52782

Middle Eastern (MID) AF: 0.582 AC: 2555 AN: 4390

European-Non Finnish (NFE) AF: 0.763 AC: 614351 AN: 805378

Other (OTH) AF: 0.719 AC: 35227 AN: 48978

GnomAD4 genome AF: 0.679 AC: 103002 AN: 151596 Hom.: 36275 Cov.: 0 AF XY: 0.684 AC XY: 50691 AN XY: 74072

African (AFR) AF: 0.479 AC: 19757 AN: 41258

American (AMR) AF: 0.731 AC: 11122 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 2296 AN: 3464

East Asian (EAS) AF: 0.782 AC: 4031 AN: 5154

South Asian (SAS) AF: 0.778 AC: 3738 AN: 4804

European-Finnish (FIN) AF: 0.800 AC: 8391 AN: 10494

Middle Eastern (MID) AF: 0.569 AC: 165 AN: 290

European-Non Finnish (NFE) AF: 0.760 AC: 51615 AN: 67910

Other (OTH) AF: 0.632 AC: 1325 AN: 2098

Alfa AF: 0.666 Hom.: 4211

Bravo AF: 0.664

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Glycogen storage disorder due to hepatic glycogen synthase deficiency (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.0040
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36023861; hg19: chr12-21692166; COSMIC: COSV53920699; COSMIC: COSV53920699;