rs78337075
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 2P and 15B. PM2BP4_ModerateBP6_Very_StrongBP7BS1
The NM_021957.4(GYS2):c.1701G>A(p.Leu567=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000169 in 1,613,910 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00087 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000096 ( 1 hom. )
Consequence
GYS2
NM_021957.4 synonymous
NM_021957.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.69
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 12-21540518-C-T is Benign according to our data. Variant chr12-21540518-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.69 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000958 (140/1461680) while in subpopulation AFR AF= 0.00382 (128/33474). AF 95% confidence interval is 0.00328. There are 1 homozygotes in gnomad4_exome. There are 68 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYS2 | NM_021957.4 | c.1701G>A | p.Leu567= | synonymous_variant | 14/16 | ENST00000261195.3 | |
GYS2 | XM_024448960.2 | c.1701G>A | p.Leu567= | synonymous_variant | 14/17 | ||
GYS2 | XM_006719063.4 | c.1470G>A | p.Leu490= | synonymous_variant | 13/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYS2 | ENST00000261195.3 | c.1701G>A | p.Leu567= | synonymous_variant | 14/16 | 1 | NM_021957.4 | P1 | |
SPX | ENST00000649016.1 | n.4001C>T | non_coding_transcript_exon_variant | 5/5 |
Frequencies
GnomAD3 genomes ? AF: 0.000874 AC: 133AN: 152112Hom.: 0 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
133
AN:
152112
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000227 AC: 57AN: 251370Hom.: 0 AF XY: 0.000228 AC XY: 31AN XY: 135838
GnomAD3 exomes
AF:
AC:
57
AN:
251370
Hom.:
AF XY:
AC XY:
31
AN XY:
135838
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000958 AC: 140AN: 1461680Hom.: 1 Cov.: 31 AF XY: 0.0000935 AC XY: 68AN XY: 727156
GnomAD4 exome
AF:
AC:
140
AN:
1461680
Hom.:
Cov.:
31
AF XY:
AC XY:
68
AN XY:
727156
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000874 AC: 133AN: 152230Hom.: 0 Cov.: 31 AF XY: 0.000833 AC XY: 62AN XY: 74412
GnomAD4 genome
?
AF:
AC:
133
AN:
152230
Hom.:
Cov.:
31
AF XY:
AC XY:
62
AN XY:
74412
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 08, 2018 | 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. - |
Likely 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 | Dec 12, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at