chr2-227888317-T-G

Variant names:

• chr2-227888317-T-G
• rs1916803
• NM_178821.3:c.114-1539T>G

Variant summary

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

The NM_178821.3(DAW1):​c.114-1539T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,030 control chromosomes in the GnomAD database, including 21,709 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 0.53 (21709 hom., cov: 33)
• Consequence: DAW1 NM_178821.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.264
• Publications: 2 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 Submitted by: G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAW1	NM_178821.3	c.114-1539T>G		intron_variant	Intron 2 of 12	ENST00000309931.3	NP_849143.1
DAW1	NM_001330004.2	c.69-1539T>G		intron_variant	Intron 3 of 13		NP_001316933.1
DAW1	NR_138459.2	n.173-1539T>G		intron_variant	Intron 2 of 13
DAW1	XM_047443536.1	c.69-1539T>G		intron_variant	Intron 4 of 14		XP_047299492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAW1	ENST00000309931.3	c.114-1539T>G		intron_variant	Intron 2 of 12	1	NM_178821.3	ENSP00000311899.2
DAW1	ENST00000440997.1	c.69-1539T>G		intron_variant	Intron 3 of 3	4		ENSP00000394853.1
DAW1	ENST00000373666.6	n.114-1539T>G		intron_variant	Intron 2 of 13	2		ENSP00000362770.2
DAW1	ENST00000454999.5	n.*55-1539T>G		intron_variant	Intron 3 of 7	3		ENSP00000403670.1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80669 AN: 151912 Hom.: 21700 Cov.: 33

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.531 AC: 80717 AN: 152030 Hom.: 21709 Cov.: 33 AF XY: 0.526 AC XY: 39085 AN XY: 74290

African (AFR) AF: 0.489 AC: 20258 AN: 41468

American (AMR) AF: 0.620 AC: 9481 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1829 AN: 3468

East Asian (EAS) AF: 0.547 AC: 2821 AN: 5158

South Asian (SAS) AF: 0.557 AC: 2684 AN: 4816

European-Finnish (FIN) AF: 0.411 AC: 4339 AN: 10546

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37584 AN: 67964

Other (OTH) AF: 0.525 AC: 1111 AN: 2116

Alfa AF: 0.551 Hom.: 12500

Bravo AF: 0.543

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.78
PhyloP100		-0.26
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: rs1916803; hg19: chr2-228753033; COSMIC: COSV59367021; COSMIC: COSV59367021;