12-21536802-G-C

Variant names:

• chr12-21536802-G-C
• rs936
• NM_021957.4:c.*152C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021957.4(GYS2):​c.*152C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000202 in 494,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000020 (0 hom.)
• Consequence: GYS2 NM_021957.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.*152C>G		3_prime_UTR	Exon 16 of 16	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.*152C>G		3_prime_UTR	Exon 16 of 16	ENSP00000261195.2	P54840
	ENSG00000285854	ENST00000647960.1		n.*2266C>G		non_coding_transcript_exon	Exon 23 of 23	ENSP00000497202.1	A0A3B3IS95
	ENSG00000285854	ENST00000647960.1		n.*2266C>G		3_prime_UTR	Exon 23 of 23	ENSP00000497202.1	A0A3B3IS95

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000202 AC: 1 AN: 494402 Hom.: 0 Cov.: 5 AF XY: 0.00 AC XY: 0 AN XY: 263212

African (AFR) AF: 0.00 AC: 0 AN: 13540

American (AMR) AF: 0.00 AC: 0 AN: 24066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15744

East Asian (EAS) AF: 0.00 AC: 0 AN: 31504

South Asian (SAS) AF: 0.00 AC: 0 AN: 48062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2106

European-Non Finnish (NFE) AF: 0.00000334 AC: 1 AN: 299204

Other (OTH) AF: 0.00 AC: 0 AN: 27786

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 32354

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.38
PhyloP100		1.2

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: rs936; hg19: chr12-21689736;