rs199894361
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_004393.6(DAG1):c.1690C>A(p.Leu564Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004393.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.1690C>A | p.Leu564Ile | missense_variant | 3/3 | ENST00000308775.7 | NP_004384.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DAG1 | ENST00000308775.7 | c.1690C>A | p.Leu564Ile | missense_variant | 3/3 | 1 | NM_004393.6 | ENSP00000312435.2 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152250Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251326Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135854
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461796Hom.: 1 Cov.: 33 AF XY: 0.0000536 AC XY: 39AN XY: 727176
GnomAD4 genome AF: 0.000118 AC: 18AN: 152368Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74506
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 10, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 09, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 20, 2017 | - - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Jul 25, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 564 of the DAG1 protein (p.Leu564Ile). This variant is present in population databases (rs199894361, gnomAD 0.2%). 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: 283248). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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