3-49530935-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004393.6(DAG1):c.424G>A(p.Gly142Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,114 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G142E) has been classified as Uncertain significance.
Frequency
Consequence
NM_004393.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.424G>A | p.Gly142Arg | missense_variant | 3/3 | ENST00000308775.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAG1 | ENST00000308775.7 | c.424G>A | p.Gly142Arg | missense_variant | 3/3 | 1 | NM_004393.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251046Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135714
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461852Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727222
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74450
ClinVar
Submissions by phenotype
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;C4511963:Autosomal recessive limb-girdle muscular dystrophy type 2P Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 25, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 142 of the DAG1 protein (p.Gly142Arg). This variant is present in population databases (rs749962207, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with DAG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 539128). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 09, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at