14-59323009-G-A
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1
The NM_001270520.2(DAAM1):c.558G>A(p.Lys186Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,613,802 control chromosomes in the GnomAD database, including 124,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.31 ( 8776 hom., cov: 31)
Exomes 𝑓: 0.39 ( 115827 hom. )
Consequence
DAAM1
NM_001270520.2 synonymous
NM_001270520.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.10
Genes affected
DAAM1 (HGNC:18142): (dishevelled associated activator of morphogenesis 1) Cell motility, adhesion, cytokinesis, and other functions of the cell cortex are mediated by reorganization of the actin cytoskeleton and several formin homology (FH) proteins have been associated with these processes. The protein encoded by this gene contains two FH domains and belongs to a novel FH protein subfamily implicated in cell polarity. A key regulator of cytoskeletal architecture, the small GTPase Rho, is activated during development by Wnt/Fz signaling to control cell polarity and movement. The protein encoded by this gene is thought to function as a scaffolding protein for the Wnt-induced assembly of a disheveled (Dvl)-Rho complex. This protein also promotes the nucleation and elongation of new actin filaments and regulates cell growth through the stabilization of microtubules. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2012]
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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=-0.45).
BP6
Variant 14-59323009-G-A is Benign according to our data. Variant chr14-59323009-G-A is described in ClinVar as [Benign]. Clinvar id is 3060418.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=2.1 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DAAM1 | NM_001270520.2 | c.558G>A | p.Lys186Lys | synonymous_variant | 6/25 | ENST00000360909.8 | NP_001257449.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DAAM1 | ENST00000360909.8 | c.558G>A | p.Lys186Lys | synonymous_variant | 6/25 | 1 | NM_001270520.2 | ENSP00000354162.3 | ||
DAAM1 | ENST00000395125.1 | c.558G>A | p.Lys186Lys | synonymous_variant | 5/25 | 1 | ENSP00000378557.1 | |||
DAAM1 | ENST00000557327.1 | n.514G>A | non_coding_transcript_exon_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.312 AC: 47458AN: 151882Hom.: 8783 Cov.: 31
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GnomAD3 exomes AF: 0.371 AC: 93067AN: 251156Hom.: 18622 AF XY: 0.378 AC XY: 51373AN XY: 135746
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GnomAD4 exome AF: 0.393 AC: 573874AN: 1461800Hom.: 115827 Cov.: 54 AF XY: 0.393 AC XY: 285689AN XY: 727204
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GnomAD4 genome AF: 0.312 AC: 47445AN: 152002Hom.: 8776 Cov.: 31 AF XY: 0.314 AC XY: 23317AN XY: 74280
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
DAAM1-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 31, 2019 | This variant is classified as 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
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at