chr18-34829079-A-C
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The ENST00000315456.10(DTNA):c.*8A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,614,158 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )
Consequence
DTNA
ENST00000315456.10 3_prime_UTR
ENST00000315456.10 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.65
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
?
Variant 18-34829079-A-C is Benign according to our data. Variant chr18-34829079-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43959.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
BS2
?
High AC in GnomAd at 16 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DTNA | NM_001386795.1 | c.1086-321A>C | intron_variant | ENST00000444659.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DTNA | ENST00000444659.6 | c.1086-321A>C | intron_variant | 5 | NM_001386795.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000269 AC: 67AN: 249522Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135368
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GnomAD4 exome AF: 0.000107 AC: 156AN: 1461816Hom.: 0 Cov.: 31 AF XY: 0.0000976 AC XY: 71AN XY: 727206
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6AN XY: 74508
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 30, 2012 | Variant classified as Uncertain Significance - Favor Benign. The *8A>C variant i n DTNA has been identified in 1/8220 European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/E VS/; dbSNP rs191973037). This variant occurs in the 3' untranslated region (3' U TR) and does not affect the coding sequence of the gene. Although this region ca n contain elements that regulate mRNA, there is no obvious predicted effect of t his variant and no other pathogenic variants have been reported in the 3' UTR re gion of the DTNA gene. Although this data supports that the *8A>C variant may be benign, additional studies are needed to fully assess its clinical significance . - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 28, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
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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