Variant 2-227871697-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_178821.3(DAW1):c.8T>A(p.Leu3His) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Consequence

DAW1
NM_178821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

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:

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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, 0.776

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAW1	NM_178821.3 linkuse as main transcript	c.8T>A	p.Leu3His	missense_variant	1/13	ENST00000309931.3	NP_849143.1	Q8N136-1A0A140VKH6
DAW1	NM_001330004.2 linkuse as main transcript	c.-90T>A		5_prime_UTR_variant	1/14		NP_001316933.1	Q8N136G5EA46B4DX89
DAW1	XM_047443536.1 linkuse as main transcript	c.-341T>A		5_prime_UTR_variant	1/15		XP_047299492.1
DAW1	NR_138459.2 linkuse as main transcript	n.67T>A		non_coding_transcript_exon_variant	1/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DAW1	ENST00000309931.3 linkuse as main transcript	c.8T>A	p.Leu3His	missense_variant	1/13	1	NM_178821.3	ENSP00000311899.2	Q8N136-1
DAW1	ENST00000440997.1 linkuse as main transcript	c.-289T>A		5_prime_UTR_variant	1/4	4		ENSP00000394853.1	C9JP90
DAW1	ENST00000373666.6 linkuse as main transcript	n.8T>A		non_coding_transcript_exon_variant	1/14	2		ENSP00000362770.2	C9JBF9
DAW1	ENST00000454999.5 linkuse as main transcript	n.8T>A		non_coding_transcript_exon_variant	1/8	3		ENSP00000403670.1	F8WCV0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152126

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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 29, 2024

The c.8T>A (p.L3H) alteration is located in exon 1 (coding exon 1) of the DAW1 gene. This alteration results from a T to A substitution at nucleotide position 8, causing the leucine (L) at amino acid position 3 to be replaced by a histidine (H). 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

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Benign

0.79

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.26

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.7

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.1

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.65

MutPred

0.40

Loss of sheet (P = 0.0025);

MVP

0.73

MPC

0.51

ClinPred

0.87

GERP RS

4.8

Varity_R

0.76

gMVP

0.73

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