Variant 2-227889965-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178821.3(DAW1):c.223G>A(p.Gly75Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000876 in 1,598,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

DAW1
NM_178821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0330

Variant links:

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 links:

DAW1 (HGNC:):

DAW1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024998754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAW1	NM_178821.3 linkuse as main transcript	c.223G>A	p.Gly75Ser	missense_variant	3/13	ENST00000309931.3	NP_849143.1	Q8N136-1A0A140VKH6
DAW1	NM_001330004.2 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	4/14		NP_001316933.1	Q8N136G5EA46B4DX89
DAW1	XM_047443536.1 linkuse as main transcript	c.178G>A	p.Gly60Ser	missense_variant	5/15		XP_047299492.1
DAW1	NR_138459.2 linkuse as main transcript	n.282G>A		non_coding_transcript_exon_variant	3/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAW1	ENST00000309931.3 linkuse as main transcript	c.223G>A	p.Gly75Ser	missense_variant	3/13	1	NM_178821.3	ENSP00000311899.2		Q8N136-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000844

AC:

AN:

236828

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128416

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000760

AC:

AN:

1446494

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719450

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000260

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000904

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152020

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

AC:

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 06, 2022

The c.223G>A (p.G75S) alteration is located in exon 3 (coding exon 3) of the DAW1 gene. This alteration results from a G to A substitution at nucleotide position 223, causing the glycine (G) at amino acid position 75 to be replaced by a serine (S). 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

0.089

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.4

DANN

Benign

0.83

DEOGEN2

Benign

0.00053

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.0078

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;.

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.078

Sift

Benign

0.74

T;T

Sift4G

Benign

0.73

T;T

Polyphen

0.0050

B;.

Vest4

0.20

MutPred

0.32

Loss of ubiquitination at K73 (P = 0.0714);.;

MVP

0.13

MPC

0.088

ClinPred

0.027

GERP RS

-6.9

Varity_R

0.027

gMVP

0.24

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over