chr3-49531744-G-A
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_004393.6(DAG1):c.1233G>A(p.Val411=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,830 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 10 hom. )
Consequence
DAG1
NM_004393.6 synonymous
NM_004393.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.546
Genes affected
DAG1 (HGNC:2666): (dystroglycan 1) This gene encodes dystroglycan, a central component of dystrophin-glycoprotein complex that links the extracellular matrix and the cytoskeleton in the skeletal muscle. The encoded preproprotein undergoes O- and N-glycosylation, and proteolytic processing to generate alpha and beta subunits. Certain mutations in this gene are known to cause distinct forms of muscular dystrophy. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Nov 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
Variant 3-49531744-G-A is Benign according to our data. Variant chr3-49531744-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 196384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49531744-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.546 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.1233G>A | p.Val411= | synonymous_variant | 3/3 | ENST00000308775.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAG1 | ENST00000308775.7 | c.1233G>A | p.Val411= | synonymous_variant | 3/3 | 1 | NM_004393.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00249 AC: 378AN: 151820Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00222 AC: 559AN: 251462Hom.: 1 AF XY: 0.00235 AC XY: 319AN XY: 135906
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GnomAD4 exome AF: 0.00334 AC: 4884AN: 1461892Hom.: 10 Cov.: 33 AF XY: 0.00338 AC XY: 2456AN XY: 727248
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GnomAD4 genome AF: 0.00249 AC: 378AN: 151938Hom.: 2 Cov.: 32 AF XY: 0.00234 AC XY: 174AN XY: 74272
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 12, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 03, 2020 | This variant is associated with the following publications: (PMID: 25671699) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | DAG1: BP4, BP7, BS2 - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 14, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 26, 2015 | - - |
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;C4511963:Autosomal recessive limb-girdle muscular dystrophy type 2P Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
DAG1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 09, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at