2-227902992-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_178821.3(DAW1):c.541-9del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,612,610 control chromosomes in the GnomAD database, including 33 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0083 (19 hom., cov: 32)
  • Exomes 𝑓: 0.00093 (14 hom.)
• Consequence: DAW1 NM_178821.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.15

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-227902992-TG-T is Benign according to our data. Variant chr2-227902992-TG-T is described in ClinVar as [Benign]. Clinvar id is 783362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00831 (1266/152330) while in subpopulation AFR AF= 0.0287 (1192/41572). AF 95% confidence interval is 0.0273. There are 19 homozygotes in gnomad4. There are 588 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAW1	NM_178821.3	c.541-9del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000309931.3
DAW1	NM_001330004.2	c.496-9del		splice_polypyrimidine_tract_variant, intron_variant
DAW1	XM_047443536.1	c.496-9del		splice_polypyrimidine_tract_variant, intron_variant
DAW1	NR_138459.2	n.600-9del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAW1	ENST00000309931.3	c.541-9del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_178821.3	P1
DAW1	ENST00000373666.6	c.541-9del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2
DAW1	ENST00000454999.5	c.*482-9del		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00828 AC: 1261 AN: 152212 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0105

GnomAD3 exomes AF: 0.00210 AC: 524 AN: 249550 Hom.: 9 AF XY: 0.00163 AC XY: 219 AN XY: 134708

Gnomad AFR exome AF: 0.0282

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000931 AC: 1360 AN: 1460280 Hom.: 14 Cov.: 30 AF XY: 0.000821 AC XY: 596 AN XY: 726278

Gnomad4 AFR exome AF: 0.0323

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000292

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000495

Gnomad4 OTH exome AF: 0.00192

GnomAD4 genome AF: 0.00831 AC: 1266 AN: 152330 Hom.: 19 Cov.: 32 AF XY: 0.00789 AC XY: 588 AN XY: 74490

Gnomad4 AFR AF: 0.0287

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.00919

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 30, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs144876495; hg19: chr2-228767708;