2-227893910-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_178821.3(DAW1):c.433C>T(p.Pro145Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000966 in 1,604,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000099 ( 0 hom. )
Consequence
DAW1
NM_178821.3 missense
NM_178821.3 missense
Scores
8
8
3
Clinical Significance
Conservation
PhyloP100: 7.16
Genes affected
DAW1 (HGNC:26383): (dynein assembly factor with WD repeats 1) Predicted to act upstream of or within several processes, including cerebrospinal fluid circulation; determination of left/right symmetry; and outer dynein arm assembly. Predicted to be located in cilium and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.759
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DAW1 | NM_178821.3 | c.433C>T | p.Pro145Ser | missense_variant | 5/13 | ENST00000309931.3 | NP_849143.1 | |
DAW1 | NM_001330004.2 | c.388C>T | p.Pro130Ser | missense_variant | 6/14 | NP_001316933.1 | ||
DAW1 | XM_047443536.1 | c.388C>T | p.Pro130Ser | missense_variant | 7/15 | XP_047299492.1 | ||
DAW1 | NR_138459.2 | n.492C>T | non_coding_transcript_exon_variant | 5/14 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000724 AC: 11AN: 152018Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000131 AC: 31AN: 237270Hom.: 0 AF XY: 0.000133 AC XY: 17AN XY: 128194
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GnomAD4 exome AF: 0.0000991 AC: 144AN: 1452604Hom.: 0 Cov.: 32 AF XY: 0.000102 AC XY: 74AN XY: 722186
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GnomAD4 genome AF: 0.0000723 AC: 11AN: 152136Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74370
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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 | Oct 06, 2021 | The c.433C>T (p.P145S) alteration is located in exon 5 (coding exon 5) of the DAW1 gene. This alteration results from a C to T substitution at nucleotide position 433, causing the proline (P) at amino acid position 145 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Pathogenic
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
T
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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