14-59322911-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001270520.2(DAAM1):c.460G>A(p.Asp154Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,610,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
DAAM1
NM_001270520.2 missense
NM_001270520.2 missense
Scores
3
10
6
Clinical Significance
Conservation
PhyloP100: 10.0
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 Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DAAM1 | ENST00000360909.8 | c.460G>A | p.Asp154Asn | missense_variant | 6/25 | 1 | NM_001270520.2 | ENSP00000354162.3 | ||
DAAM1 | ENST00000395125.1 | c.460G>A | p.Asp154Asn | missense_variant | 5/25 | 1 | ENSP00000378557.1 | |||
DAAM1 | ENST00000557327.1 | n.416G>A | non_coding_transcript_exon_variant | 3/3 | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152114Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249844Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 134998
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1458620Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 725060
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74308
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 01, 2022 | The c.460G>A (p.D154N) alteration is located in exon 6 (coding exon 5) of the DAAM1 gene. This alteration results from a G to A substitution at nucleotide position 460, causing the aspartic acid (D) at amino acid position 154 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;D
Eigen
Uncertain
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;L
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MVP
MPC
0.29
ClinPred
D
GERP RS
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gMVP
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