rs144776465
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001386795.1(DTNA):c.1404G>A(p.Ala468=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,613,880 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 2 hom. )
Consequence
DTNA
NM_001386795.1 synonymous
NM_001386795.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.59
Genes affected
DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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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=-0.76).
BP6
Variant 18-34848353-G-A is Benign according to our data. Variant chr18-34848353-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-34848353-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-1.6 with no splicing effect.
BS2
High AC in GnomAd4 at 40 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.1404G>A | p.Ala468= | synonymous_variant | 14/23 | ENST00000444659.6 | NP_001373724.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.1404G>A | p.Ala468= | synonymous_variant | 14/23 | 5 | NM_001386795.1 | ENSP00000405819 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000263 AC: 40AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000211 AC: 53AN: 251268Hom.: 1 AF XY: 0.000228 AC XY: 31AN XY: 135804
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GnomAD4 exome AF: 0.000260 AC: 380AN: 1461714Hom.: 2 Cov.: 31 AF XY: 0.000294 AC XY: 214AN XY: 727160
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GnomAD4 genome AF: 0.000263 AC: 40AN: 152166Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74334
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:3
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 05, 2020 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 06, 2024 | - - |
Left ventricular noncompaction 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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DANN
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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