chr12-21536966-T-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_021957.4(GYS2):āc.2100A>Gā(p.Glu700=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000069 ( 0 hom. )
Consequence
GYS2
NM_021957.4 synonymous
NM_021957.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.90
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 Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
Variant 12-21536966-T-C is Benign according to our data. Variant chr12-21536966-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 558809.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=2.9 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYS2 | NM_021957.4 | c.2100A>G | p.Glu700= | synonymous_variant | 16/16 | ENST00000261195.3 | |
LOC124902896 | XR_007063240.1 | n.519-80T>C | intron_variant, non_coding_transcript_variant | ||||
GYS2 | XM_024448960.2 | c.2100A>G | p.Glu700= | synonymous_variant | 16/17 | ||
GYS2 | XM_006719063.4 | c.1869A>G | p.Glu623= | synonymous_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYS2 | ENST00000261195.3 | c.2100A>G | p.Glu700= | synonymous_variant | 16/16 | 1 | NM_021957.4 | P1 | |
SPX | ENST00000537527.1 | n.472-80T>C | intron_variant, non_coding_transcript_variant | 3 | |||||
SPX | ENST00000649016.1 | n.529-80T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251084Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135676
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GnomAD4 exome AF: 0.00000686 AC: 10AN: 1458438Hom.: 0 Cov.: 30 AF XY: 0.00000964 AC XY: 7AN XY: 725830
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152200Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Oct 23, 2015 | - - |
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