rs76713874
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001386795.1(DTNA):c.2162+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 1,613,800 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0079 ( 12 hom., cov: 32)
Exomes 𝑓: 0.0093 ( 72 hom. )
Consequence
DTNA
NM_001386795.1 intron
NM_001386795.1 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.32
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 -16 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.94).
BP6
Variant 18-34879733-G-A is Benign according to our data. Variant chr18-34879733-G-A is described in ClinVar as [Benign]. Clinvar id is 36028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-34879733-G-A is described in Lovd as [Likely_benign]. Variant chr18-34879733-G-A is described in Lovd as [Benign].
BS2
High AC in GnomAd4 at 1202 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.2162+14G>A | intron_variant | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.2162+14G>A | intron_variant | 5 | NM_001386795.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.00790 AC: 1202AN: 152136Hom.: 12 Cov.: 32
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GnomAD3 exomes AF: 0.00727 AC: 1824AN: 251018Hom.: 13 AF XY: 0.00740 AC XY: 1004AN XY: 135662
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GnomAD4 exome AF: 0.00934 AC: 13652AN: 1461546Hom.: 72 Cov.: 30 AF XY: 0.00931 AC XY: 6766AN XY: 727052
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GnomAD4 genome AF: 0.00789 AC: 1202AN: 152254Hom.: 12 Cov.: 32 AF XY: 0.00783 AC XY: 583AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Left ventricular noncompaction 1 Benign:4
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 12, 2022 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Aug 22, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 12, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 02, 2012 | - - |
Cardiomyopathy Benign:1
Benign, no assertion criteria provided | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 04, 2015 | - - |
Computational scores
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Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at