3-49532652-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004393.6(DAG1):c.2141G>A(p.Arg714Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R714L) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.2141G>A | p.Arg714Gln | missense_variant | 3/3 | ENST00000308775.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAG1 | ENST00000308775.7 | c.2141G>A | p.Arg714Gln | missense_variant | 3/3 | 1 | NM_004393.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250780Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135566
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461752Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727150
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74338
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 26, 2019 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;C4511963:Autosomal recessive limb-girdle muscular dystrophy type 2P Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 714 of the DAG1 protein (p.Arg714Gln). This variant is present in population databases (rs201488118, gnomAD 0.02%). 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: 471772). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DAG1 protein function with a negative predictive value of 80%. 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