rs36023861

Positions:

• chr12-21539232-CAA-C
• chr12-21539232-CAA-CA
• chr12-21539232-CAA-CAAA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021957.4(GYS2):​c.1890+24_1890+25del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,273,098 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: GYS2 NM_021957.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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]

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYS2	NM_021957.4	c.1890+24_1890+25del		intron_variant		ENST00000261195.3
GYS2	XM_006719063.4	c.1659+24_1659+25del		intron_variant
GYS2	XM_024448960.2	c.1890+24_1890+25del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS2	ENST00000261195.3	c.1890+24_1890+25del		intron_variant		1	NM_021957.4	P1
SPX	ENST00000649016.1	n.2723_2724del		non_coding_transcript_exon_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151558 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000229 AC: 257 AN: 1121540 Hom.: 0 AF XY: 0.000232 AC XY: 133 AN XY: 573590

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000463

Gnomad4 ASJ exome AF: 0.0000838

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000465

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000253

Gnomad4 OTH exome AF: 0.000184

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151558 Hom.: 0 Cov.: 0 AF XY: 0.0000135 AC XY: 1 AN XY: 73992

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000350 Hom.: 4211

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs36023861; hg19: chr12-21692166;