rs886038665

Variant names:

• chr12-21568899-T-C
• rs886038665
• NM_021957.4:c.789A>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_021957.4(GYS2):​c.789A>G​(p.Ala263Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GYS2 NM_021957.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0500

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:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 12-21568899-T-C is Benign according to our data. Variant chr12-21568899-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 261472.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.05 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYS2	NM_021957.4	c.789A>G	p.Ala263Ala	synonymous_variant	Exon 5 of 16	ENST00000261195.3	NP_068776.2
GYS2	XM_024448960.2	c.789A>G	p.Ala263Ala	synonymous_variant	Exon 5 of 17		XP_024304728.1
GYS2	XM_006719063.4	c.558A>G	p.Ala186Ala	synonymous_variant	Exon 4 of 15		XP_006719126.1
GYS2	XM_017019245.3	c.789A>G	p.Ala263Ala	synonymous_variant	Exon 5 of 9		XP_016874734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYS2	ENST00000261195.3	c.789A>G	p.Ala263Ala	synonymous_variant	Exon 5 of 16	1	NM_021957.4	ENSP00000261195.2
ENSG00000285854	ENST00000647960.1	n.*791A>G		non_coding_transcript_exon_variant	Exon 12 of 23			ENSP00000497202.1
ENSG00000285854	ENST00000647960.1	n.*791A>G		3_prime_UTR_variant	Exon 12 of 23			ENSP00000497202.1
ENSG00000285854	ENST00000648372.1	n.716A>G		non_coding_transcript_exon_variant	Exon 5 of 11

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.3
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs886038665; hg19: chr12-21721833;