chr2-227905013-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178821.3(DAW1):c.733G>A(p.Val245Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,332 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
DAW1
NM_178821.3 missense
NM_178821.3 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 3.49
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DAW1 | NM_178821.3 | c.733G>A | p.Val245Met | missense_variant | 8/13 | ENST00000309931.3 | |
DAW1 | NM_001330004.2 | c.688G>A | p.Val230Met | missense_variant | 9/14 | ||
DAW1 | XM_047443536.1 | c.688G>A | p.Val230Met | missense_variant | 10/15 | ||
DAW1 | NR_138459.2 | n.792G>A | non_coding_transcript_exon_variant | 8/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAW1 | ENST00000309931.3 | c.733G>A | p.Val245Met | missense_variant | 8/13 | 1 | NM_178821.3 | P1 | |
DAW1 | ENST00000373666.6 | c.733G>A | p.Val245Met | missense_variant, NMD_transcript_variant | 8/14 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251158Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135754
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461126Hom.: 0 Cov.: 30 AF XY: 0.0000275 AC XY: 20AN XY: 726902
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GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74350
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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 | Nov 21, 2023 | The c.733G>A (p.V245M) alteration is located in exon 8 (coding exon 8) of the DAW1 gene. This alteration results from a G to A substitution at nucleotide position 733, causing the valine (V) at amino acid position 245 to be replaced by a methionine (M). 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
Uncertain
Cadd
Benign
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
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