rs139882761
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_021957.4(GYS2):c.1251C>T(p.Asn417=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000232 in 1,606,610 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00030 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00022 ( 0 hom. )
Consequence
GYS2
NM_021957.4 synonymous
NM_021957.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.07
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant 12-21559148-G-A is Benign according to our data. Variant chr12-21559148-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 261465.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2, Likely_benign=1}.
BP7
?
Synonymous conserved (PhyloP=3.07 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYS2 | NM_021957.4 | c.1251C>T | p.Asn417= | synonymous_variant | 10/16 | ENST00000261195.3 | |
GYS2 | XM_024448960.2 | c.1251C>T | p.Asn417= | synonymous_variant | 10/17 | ||
GYS2 | XM_006719063.4 | c.1020C>T | p.Asn340= | synonymous_variant | 9/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYS2 | ENST00000261195.3 | c.1251C>T | p.Asn417= | synonymous_variant | 10/16 | 1 | NM_021957.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000303 AC: 46AN: 151828Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000475 AC: 119AN: 250704Hom.: 0 AF XY: 0.000398 AC XY: 54AN XY: 135546
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GnomAD4 exome AF: 0.000224 AC: 326AN: 1454782Hom.: 0 Cov.: 27 AF XY: 0.000238 AC XY: 172AN XY: 724060
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GnomAD4 genome ? AF: 0.000303 AC: 46AN: 151828Hom.: 1 Cov.: 32 AF XY: 0.000297 AC XY: 22AN XY: 74138
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Glycogen storage disorder due to hepatic glycogen synthase deficiency Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at