rs936

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-21536802-G-A
• chr12-21536802-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021957.4(GYS2):​c.*152C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 645,728 control chromosomes in the GnomAD database, including 108,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (20348 hom., cov: 32)
  • Exomes 𝑓: 0.59 (87865 hom.)
• Consequence: GYS2 NM_021957.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-21536802-G-A is Benign according to our data. Variant chr12-21536802-G-A is described in ClinVar as Benign. ClinVar VariationId is 307985.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.716 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.*152C>T		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>T		3_prime_UTR	Exon 16 of 16	ENSP00000261195.2	P54840
	ENSG00000285854	ENST00000647960.1		n.*2266C>T		non_coding_transcript_exon	Exon 23 of 23	ENSP00000497202.1	A0A3B3IS95
	ENSG00000285854	ENST00000647960.1		n.*2266C>T		3_prime_UTR	Exon 23 of 23	ENSP00000497202.1	A0A3B3IS95

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73439 AN: 151920 Hom.: 20339 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.736

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.588 AC: 290422 AN: 493690 Hom.: 87865 Cov.: 5 AF XY: 0.592 AC XY: 155704 AN XY: 262802

African (AFR) AF: 0.191 AC: 2578 AN: 13530

American (AMR) AF: 0.657 AC: 15796 AN: 24026

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 7960 AN: 15722

East Asian (EAS) AF: 0.782 AC: 24637 AN: 31486

South Asian (SAS) AF: 0.677 AC: 32499 AN: 47998

European-Finnish (FIN) AF: 0.574 AC: 18567 AN: 32346

Middle Eastern (MID) AF: 0.385 AC: 810 AN: 2104

European-Non Finnish (NFE) AF: 0.577 AC: 172366 AN: 298746

Other (OTH) AF: 0.548 AC: 15209 AN: 27732

GnomAD4 genome AF: 0.483 AC: 73469 AN: 152038 Hom.: 20348 Cov.: 32 AF XY: 0.491 AC XY: 36495 AN XY: 74306

African (AFR) AF: 0.201 AC: 8325 AN: 41458

American (AMR) AF: 0.595 AC: 9102 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1756 AN: 3470

East Asian (EAS) AF: 0.735 AC: 3805 AN: 5174

South Asian (SAS) AF: 0.697 AC: 3362 AN: 4822

European-Finnish (FIN) AF: 0.578 AC: 6098 AN: 10550

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39525 AN: 67964

Other (OTH) AF: 0.470 AC: 993 AN: 2112

Alfa AF: 0.543 Hom.: 32354

Bravo AF: 0.471

Asia WGS AF: 0.661 AC: 2291 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Glycogen storage disorder due to hepatic glycogen synthase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.22
PhyloP100		1.2
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: rs936; hg19: chr12-21689736;