rs201739236
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_004408.4(DNM1):c.1782-9A>G 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 0.000144 in 1,598,724 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 0.00080 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000075 ( 0 hom. )
Consequence
DNM1
NM_004408.4 splice_polypyrimidine_tract, intron
NM_004408.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00001518
2
Clinical Significance
Conservation
PhyloP100: -0.895
Genes affected
DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 9-128247366-A-G is Benign according to our data. Variant chr9-128247366-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 390291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNM1 | NM_004408.4 | c.1782-9A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000372923.8 | NP_004399.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNM1 | ENST00000372923.8 | c.1782-9A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_004408.4 | ENSP00000362014 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000795 AC: 121AN: 152156Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000203 AC: 50AN: 246428Hom.: 0 AF XY: 0.000143 AC XY: 19AN XY: 133254
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GnomAD4 exome AF: 0.0000747 AC: 108AN: 1446450Hom.: 0 Cov.: 29 AF XY: 0.0000697 AC XY: 50AN XY: 717352
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GnomAD4 genome AF: 0.000801 AC: 122AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53AN XY: 74466
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | DNM1: BS1 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 09, 2021 | - - |
Developmental and epileptic encephalopathy, 31A Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 06, 2024 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 26, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Calibrated prediction
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
Find out detailed SpliceAI scores and Pangolin per-transcript scores at