rs1721359

Variant names:

• chr2-227887158-G-A
• rs1721359
• NM_178821.3:c.113+1735G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178821.3(DAW1):​c.113+1735G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 152,092 control chromosomes in the GnomAD database, including 40,037 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (40037 hom., cov: 31)
• Consequence: DAW1 NM_178821.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 52

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, G2P, Ambry Genetics
• visceral heterotaxy

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178821.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAW1	NM_178821.3	MANE Select	c.113+1735G>A		intron	N/A	NP_849143.1	Q8N136-1
	DAW1	NM_001330004.2		c.68+1735G>A		intron	N/A	NP_001316933.1
	DAW1	NR_138459.2		n.172+1735G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAW1	ENST00000309931.3	TSL:1 MANE Select	c.113+1735G>A		intron	N/A	ENSP00000311899.2	Q8N136-1
	DAW1	ENST00000947949.1		c.113+1735G>A		intron	N/A	ENSP00000618008.1
	DAW1	ENST00000440997.1	TSL:4	c.68+1735G>A		intron	N/A	ENSP00000394853.1	C9JP90

Frequencies

GnomAD3 genomes AF: 0.724 AC: 110003 AN: 151976 Hom.: 40035 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.742

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.724 AC: 110048 AN: 152092 Hom.: 40037 Cov.: 31 AF XY: 0.720 AC XY: 53543 AN XY: 74350

African (AFR) AF: 0.658 AC: 27272 AN: 41474

American (AMR) AF: 0.782 AC: 11959 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2589 AN: 3472

East Asian (EAS) AF: 0.565 AC: 2922 AN: 5170

South Asian (SAS) AF: 0.712 AC: 3429 AN: 4816

European-Finnish (FIN) AF: 0.715 AC: 7558 AN: 10566

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51934 AN: 67988

Other (OTH) AF: 0.738 AC: 1559 AN: 2112

Alfa AF: 0.751 Hom.: 8052

Bravo AF: 0.726

Asia WGS AF: 0.613 AC: 2132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.6
DANN	Benign	0.46
PhyloP100		0.031
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1721359; hg19: chr2-228751874;