Variant chr2-227898261-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178821.3(DAW1):c.520A>G(p.Arg174Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000577 in 1,559,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000043 ( 0 hom. )

Consequence

DAW1
NM_178821.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.805

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4132679).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAW1	NM_178821.3 link	c.520A>G	p.Arg174Gly	missense_variant	6/13	ENST00000309931.3	NP_849143.1	Q8N136-1A0A140VKH6
DAW1	NM_001330004.2 link	c.475A>G	p.Arg159Gly	missense_variant	7/14		NP_001316933.1	Q8N136G5EA46B4DX89
DAW1	XM_047443536.1 link	c.475A>G	p.Arg159Gly	missense_variant	8/15		XP_047299492.1
DAW1	NR_138459.2 link	n.579A>G		non_coding_transcript_exon_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DAW1	ENST00000309931.3 link	c.520A>G	p.Arg174Gly	missense_variant	6/13	1	NM_178821.3	ENSP00000311899.2	Q8N136-1
DAW1	ENST00000373666.6 link	n.520A>G		non_coding_transcript_exon_variant	6/14	2		ENSP00000362770.2	C9JBF9
DAW1	ENST00000454999.5 link	n.*461A>G		non_coding_transcript_exon_variant	7/8	3		ENSP00000403670.1	F8WCV0
DAW1	ENST00000454999.5 link	n.*461A>G		3_prime_UTR_variant	7/8	3		ENSP00000403670.1	F8WCV0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

244768

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000912

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000426

AC:

AN:

1407364

Hom.:

Cov.:

AF XY:

0.00000573

AC XY:

AN XY:

698442

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000116

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:

9.25e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151930

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000656

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:

0.0000302

ExAC

AF:

0.00000824

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

Jun 07, 2024

The c.520A>G (p.R174G) alteration is located in exon 6 (coding exon 6) of the DAW1 gene. This alteration results from a A to G substitution at nucleotide position 520, causing the arginine (R) at amino acid position 174 to be replaced by a glycine (G). 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

0.29

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.026

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.73

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.037

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.17

Sift

Benign

0.41

Sift4G

Benign

0.55

Polyphen

0.044

Vest4

0.67

MutPred

0.46

Loss of methylation at R174 (P = 0.0251);

MVP

0.45

MPC

0.13

ClinPred

0.19

GERP RS

1.4

Varity_R

0.40

gMVP

0.33

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