rs148634653
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001278464.2(DNM1L):c.2007C>T(p.Leu669=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,613,430 control chromosomes in the GnomAD database, including 517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 44 hom., cov: 33)
Exomes 𝑓: 0.023 ( 473 hom. )
Consequence
DNM1L
NM_001278464.2 synonymous
NM_001278464.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.150
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 -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 12-32740492-C-T is Benign according to our data. Variant chr12-32740492-C-T is described in ClinVar as [Benign]. Clinvar id is 137128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.15 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0176 (2673/152262) while in subpopulation NFE AF= 0.0283 (1926/68016). AF 95% confidence interval is 0.0273. There are 44 homozygotes in gnomad4. There are 1277 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 44 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1L | NM_001278464.2 | c.2007C>T | p.Leu669= | synonymous_variant | 19/21 | ENST00000553257.6 | |
DNM1L | NM_012062.5 | c.1968C>T | p.Leu656= | synonymous_variant | 18/20 | ENST00000549701.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1L | ENST00000553257.6 | c.2007C>T | p.Leu669= | synonymous_variant | 19/21 | 2 | NM_001278464.2 | ||
DNM1L | ENST00000549701.6 | c.1968C>T | p.Leu656= | synonymous_variant | 18/20 | 1 | NM_012062.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0176 AC: 2676AN: 152144Hom.: 44 Cov.: 33
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GnomAD3 exomes AF: 0.0180 AC: 4515AN: 250426Hom.: 62 AF XY: 0.0187 AC XY: 2536AN XY: 135350
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GnomAD4 exome AF: 0.0227 AC: 33120AN: 1461168Hom.: 473 Cov.: 30 AF XY: 0.0225 AC XY: 16389AN XY: 726870
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GnomAD4 genome ? AF: 0.0176 AC: 2673AN: 152262Hom.: 44 Cov.: 33 AF XY: 0.0172 AC XY: 1277AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2012 | 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:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 04, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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