rs149564053
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_004393.6(DAG1):āc.2520T>Cā(p.Thr840=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,613,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00085 ( 0 hom., cov: 32)
Exomes š: 0.000099 ( 0 hom. )
Consequence
DAG1
NM_004393.6 synonymous
NM_004393.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.35
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
?
Variant 3-49533031-T-C is Benign according to our data. Variant chr3-49533031-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 284298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.35 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAG1 | NM_004393.6 | c.2520T>C | p.Thr840= | synonymous_variant | 3/3 | ENST00000308775.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAG1 | ENST00000308775.7 | c.2520T>C | p.Thr840= | synonymous_variant | 3/3 | 1 | NM_004393.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000844 AC: 128AN: 151718Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000235 AC: 59AN: 251190Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135800
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GnomAD4 exome AF: 0.0000992 AC: 145AN: 1461870Hom.: 0 Cov.: 34 AF XY: 0.0000866 AC XY: 63AN XY: 727230
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GnomAD4 genome ? AF: 0.000850 AC: 129AN: 151836Hom.: 0 Cov.: 32 AF XY: 0.000835 AC XY: 62AN XY: 74212
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 11, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2020 | - - |
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 20, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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