18-34851875-C-T
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_001386795.1(DTNA):c.1479C>T(p.Ile493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,613,888 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 (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000046 ( 0 hom. )
Consequence
DTNA
NM_001386795.1 synonymous
NM_001386795.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.233
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.26).
BP6
Variant 18-34851875-C-T is Benign according to our data. Variant chr18-34851875-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 466626.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.233 with no splicing effect.
BS2
High AC in GnomAd4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.1479C>T | p.Ile493= | synonymous_variant | 15/23 | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.1479C>T | p.Ile493= | synonymous_variant | 15/23 | 5 | NM_001386795.1 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152184Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251214Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135748
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GnomAD4 exome AF: 0.0000458 AC: 67AN: 1461704Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727164
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GnomAD4 genome AF: 0.0000657 AC: 10AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74342
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DTNA-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 08, 2021 | 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). - |
Left ventricular noncompaction 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 17, 2022 | - - |
Computational scores
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BayesDel_noAF
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at