rs3765094
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_021957.4(GYS2):c.304-17T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000757 in 1,598,316 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.00095 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00074 ( 13 hom. )
Consequence
GYS2
NM_021957.4 splice_polypyrimidine_tract, intron
NM_021957.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.11
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 12-21576074-A-G is Benign according to our data. Variant chr12-21576074-A-G is described in ClinVar as [Benign]. Clinvar id is 261470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000952 (145/152320) while in subpopulation EAS AF= 0.026 (135/5190). AF 95% confidence interval is 0.0224. There are 1 homozygotes in gnomad4. There are 79 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYS2 | NM_021957.4 | c.304-17T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000261195.3 | |||
GYS2 | XM_006719063.4 | c.73-17T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
GYS2 | XM_017019245.3 | c.304-17T>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
GYS2 | XM_024448960.2 | c.304-17T>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYS2 | ENST00000261195.3 | c.304-17T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_021957.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000959 AC: 146AN: 152202Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00223 AC: 551AN: 247470Hom.: 7 AF XY: 0.00200 AC XY: 268AN XY: 134142
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GnomAD4 exome AF: 0.000737 AC: 1065AN: 1445996Hom.: 13 Cov.: 28 AF XY: 0.000729 AC XY: 525AN XY: 720582
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 17, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Glycogen storage disorder due to hepatic glycogen synthase deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 03, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -17
Find out detailed SpliceAI scores and Pangolin per-transcript scores at