chr12-21536998-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_021957.4(GYS2):c.2068G>A(p.Val690Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V690F) has been classified as Likely benign.
Frequency
Consequence
NM_021957.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GYS2 | NM_021957.4 | c.2068G>A | p.Val690Ile | missense_variant | 16/16 | ENST00000261195.3 | |
LOC124902896 | XR_007063240.1 | n.519-48C>T | intron_variant, non_coding_transcript_variant | ||||
GYS2 | XM_024448960.2 | c.2068G>A | p.Val690Ile | missense_variant | 16/17 | ||
GYS2 | XM_006719063.4 | c.1837G>A | p.Val613Ile | missense_variant | 15/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GYS2 | ENST00000261195.3 | c.2068G>A | p.Val690Ile | missense_variant | 16/16 | 1 | NM_021957.4 | P1 | |
SPX | ENST00000537527.1 | n.472-48C>T | intron_variant, non_coding_transcript_variant | 3 | |||||
SPX | ENST00000649016.1 | n.529-48C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251154Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135738
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461674Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7AN XY: 727162
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Glycogen storage disorder due to hepatic glycogen synthase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 19, 2023 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 690 of the GYS2 protein (p.Val690Ile). This variant is present in population databases (rs148461282, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GYS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at