2-227885378-G-A

Position:

• chr2-227885378-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_178821.3(DAW1):​c.68G>A​(p.Gly23Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000552 in 1,448,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: DAW1 NM_178821.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

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]

DAW1 (HGNC:):

ACMG classification

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	Protein	UniProt
DAW1	NM_178821.3	c.68G>A	p.Gly23Glu	missense_variant	2/13	ENST00000309931.3	NP_849143.1
DAW1	NM_001330004.2	c.23G>A	p.Gly8Glu	missense_variant	3/14		NP_001316933.1
DAW1	XM_047443536.1	c.23G>A	p.Gly8Glu	missense_variant	4/15		XP_047299492.1
DAW1	NR_138459.2	n.127G>A		non_coding_transcript_exon_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAW1	ENST00000309931.3	c.68G>A	p.Gly23Glu	missense_variant	2/13	1	NM_178821.3	ENSP00000311899.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000552 AC: 8 AN: 1448734 Hom.: 0 Cov.: 29 AF XY: 0.00000278 AC XY: 2 AN XY: 720480

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000723

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.68G>A (p.G23E) alteration is located in exon 2 (coding exon 2) of the DAW1 gene. This alteration results from a G to A substitution at nucleotide position 68, causing the glycine (G) at amino acid position 23 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.32
Sift	Benign	0.078	T;D
Sift4G	Benign	0.12	T;D
Polyphen		0.99	D;.
Vest4		0.53
MutPred		0.43		Loss of sheet (P = 0.0315);.;
MVP		0.71
MPC		0.21
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.45
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1179766590; hg19: chr2-228750094; COSMIC: COSV59364716; COSMIC: COSV59364716;