chr12-32731143-G-A
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1
The NM_001278464.2(DNM1L):c.1239+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,778 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 1 hom. )
Consequence
DNM1L
NM_001278464.2 intron
NM_001278464.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0620
Genes affected
DNM1L (HGNC:2973): (dynamin 1 like) This gene encodes a member of the dynamin superfamily of GTPases. The encoded protein mediates mitochondrial and peroxisomal division, and is involved in developmentally regulated apoptosis and programmed necrosis. Dysfunction of this gene is implicated in several neurological disorders, including Alzheimer's disease. Mutations in this gene are associated with the autosomal dominant disorder, encephalopathy, lethal, due to defective mitochondrial and peroxisomal fission (EMPF). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2013]
YARS2 (HGNC:24249): (tyrosyl-tRNA synthetase 2) This gene encodes a mitochondrial protein that catalyzes the attachment of tyrosine to tRNA(Tyr). Mutations in this gene are associated with myopathy with lactic acidosis and sideroblastic anemia type 2 (MLASA2). [provided by RefSeq, Jan 2011]
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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=-0.55).
BP6
?
Variant 12-32731143-G-A is Benign according to our data. Variant chr12-32731143-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 214302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000287 (42/1461670) while in subpopulation AMR AF= 0.000626 (28/44724). AF 95% confidence interval is 0.000444. There are 1 homozygotes in gnomad4_exome. There are 15 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1L | NM_001278464.2 | c.1239+9G>A | intron_variant | ENST00000553257.6 | |||
DNM1L | NM_012062.5 | c.1200+9G>A | intron_variant | ENST00000549701.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1L | ENST00000549701.6 | c.1200+9G>A | intron_variant | 1 | NM_012062.5 | ||||
DNM1L | ENST00000553257.6 | c.1239+9G>A | intron_variant | 2 | NM_001278464.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151990Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251350Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135858
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GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461670Hom.: 1 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727148
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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
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 31, 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
DNM1L-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 13, 2019 | 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). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at