2-227907247-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_178821.3(DAW1):c.968C>G(p.Ala323Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,611,306 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 1 hom. )
Consequence
DAW1
NM_178821.3 missense
NM_178821.3 missense
Scores
9
10
Clinical Significance
Conservation
PhyloP100: 4.26
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.968C>G | p.Ala323Gly | missense_variant | 10/13 | ENST00000309931.3 | |
DAW1 | NM_001330004.2 | c.923C>G | p.Ala308Gly | missense_variant | 11/14 | ||
DAW1 | XM_047443536.1 | c.923C>G | p.Ala308Gly | missense_variant | 12/15 | ||
DAW1 | NR_138459.2 | n.1027C>G | non_coding_transcript_exon_variant | 10/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DAW1 | ENST00000309931.3 | c.968C>G | p.Ala323Gly | missense_variant | 10/13 | 1 | NM_178821.3 | P1 | |
DAW1 | ENST00000373666.6 | c.968C>G | p.Ala323Gly | missense_variant, NMD_transcript_variant | 10/14 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249808Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135004
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459152Hom.: 1 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 725878
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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 | Feb 11, 2022 | The c.968C>G (p.A323G) alteration is located in exon 10 (coding exon 10) of the DAW1 gene. This alteration results from a C to G substitution at nucleotide position 968, causing the alanine (A) at amino acid position 323 to be replaced by a glycine (G). 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
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
N
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Gain of glycosylation at S322 (P = 0.0624);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at