rs184731250
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001278464.2(DNM1L):c.1119-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.007 in 1,613,590 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0064 ( 8 hom., cov: 32)
Exomes 𝑓: 0.0071 ( 50 hom. )
Consequence
DNM1L
NM_001278464.2 splice_polypyrimidine_tract, intron
NM_001278464.2 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.25
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.52).
BP6
?
Variant 12-32730998-C-T is Benign according to our data. Variant chr12-32730998-C-T is described in ClinVar as [Benign]. Clinvar id is 260164.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00642 (978/152246) while in subpopulation AMR AF= 0.0109 (166/15290). AF 95% confidence interval is 0.00951. There are 8 homozygotes in gnomad4. There are 501 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 8 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNM1L | NM_001278464.2 | c.1119-16C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000553257.6 | |||
DNM1L | NM_012062.5 | c.1080-16C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000549701.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNM1L | ENST00000549701.6 | c.1080-16C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_012062.5 | ||||
DNM1L | ENST00000553257.6 | c.1119-16C>T | splice_polypyrimidine_tract_variant, intron_variant | 2 | NM_001278464.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00644 AC: 979AN: 152130Hom.: 8 Cov.: 32
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GnomAD3 exomes AF: 0.00673 AC: 1691AN: 251298Hom.: 12 AF XY: 0.00686 AC XY: 932AN XY: 135816
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GnomAD4 exome AF: 0.00706 AC: 10317AN: 1461344Hom.: 50 Cov.: 32 AF XY: 0.00691 AC XY: 5026AN XY: 726976
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GnomAD4 genome ? AF: 0.00642 AC: 978AN: 152246Hom.: 8 Cov.: 32 AF XY: 0.00673 AC XY: 501AN XY: 74438
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
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