chr12-21536802-G-A
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
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
NM_021957.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.15
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 id 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.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYS2 | NM_021957.4 | c.*152C>T | 3_prime_UTR_variant | 16/16 | ENST00000261195.3 | ||
LOC124902896 | XR_007063240.1 | n.519-244G>A | intron_variant, non_coding_transcript_variant | ||||
GYS2 | XM_006719063.4 | c.*152C>T | 3_prime_UTR_variant | 15/15 | |||
GYS2 | XM_024448960.2 | c.*42+110C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYS2 | ENST00000261195.3 | c.*152C>T | 3_prime_UTR_variant | 16/16 | 1 | NM_021957.4 | P1 | ||
SPX | ENST00000537527.1 | n.472-244G>A | intron_variant, non_coding_transcript_variant | 3 | |||||
SPX | ENST00000649016.1 | n.529-244G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.483 AC: 73439AN: 151920Hom.: 20339 Cov.: 32
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GnomAD4 exome AF: 0.588 AC: 290422AN: 493690Hom.: 87865 Cov.: 5 AF XY: 0.592 AC XY: 155704AN XY: 262802
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GnomAD4 genome AF: 0.483 AC: 73469AN: 152038Hom.: 20348 Cov.: 32 AF XY: 0.491 AC XY: 36495AN XY: 74306
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Glycogen storage disorder due to hepatic glycogen synthase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 29, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at