rs2288019

Variant names:

• chr16-84176028-C-G
• rs2288019
• NM_178452.6:c.1794C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-84176028-C-G
• chr16-84176028-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_178452.6(DNAAF1):​c.1794C>G​(p.Leu598Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 1,613,586 control chromosomes in the GnomAD database, including 212,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20081 hom., cov: 32)
  • Exomes 𝑓: 0.51 (192179 hom.)
• Consequence: DNAAF1 NM_178452.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -2.50
• Publications: 26 publications found

Genes affected

DNAAF1 (HGNC:30539): (dynein axonemal assembly factor 1) The protein encoded by this gene is cilium-specific and is required for the stability of the ciliary architecture. It is involved in the regulation of microtubule-based cilia and actin-based brush border microvilli. Mutations in this gene are associated with primary ciliary dyskinesia-13. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

DNAAF1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-84176028-C-G is Benign according to our data. Variant chr16-84176028-C-G is described in ClinVar as Benign. ClinVar VariationId is 163086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178452.6. 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
	DNAAF1	NM_178452.6	MANE Select	c.1794C>G	p.Leu598Leu	synonymous	Exon 11 of 12	NP_848547.4
	DNAAF1	NM_001318756.1		c.1086C>G	p.Leu362Leu	synonymous	Exon 7 of 8	NP_001305685.1	Q8NEP3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF1	ENST00000378553.10	TSL:1 MANE Select	c.1794C>G	p.Leu598Leu	synonymous	Exon 11 of 12	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000963697.1		c.1800C>G	p.Leu600Leu	synonymous	Exon 11 of 13	ENSP00000633756.1
	DNAAF1	ENST00000963694.1		c.1794C>G	p.Leu598Leu	synonymous	Exon 11 of 13	ENSP00000633753.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78113 AN: 151868 Hom.: 20039 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.583

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.522

GnomAD2 exomes AF: 0.528 AC: 132579 AN: 251306 AF XY: 0.529

Gnomad AFR exome AF: 0.517

Gnomad AMR exome AF: 0.581

Gnomad ASJ exome AF: 0.520

Gnomad EAS exome AF: 0.522

Gnomad FIN exome AF: 0.473

Gnomad NFE exome AF: 0.509

Gnomad OTH exome AF: 0.535

GnomAD4 exome AF: 0.512 AC: 748190 AN: 1461600 Hom.: 192179 Cov.: 60 AF XY: 0.513 AC XY: 373279 AN XY: 727118

African (AFR) AF: 0.514 AC: 17198 AN: 33468

American (AMR) AF: 0.580 AC: 25927 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 13734 AN: 26134

East Asian (EAS) AF: 0.524 AC: 20789 AN: 39698

South Asian (SAS) AF: 0.581 AC: 50142 AN: 86254

European-Finnish (FIN) AF: 0.477 AC: 25443 AN: 53386

Middle Eastern (MID) AF: 0.542 AC: 3126 AN: 5768

European-Non Finnish (NFE) AF: 0.504 AC: 560710 AN: 1111790

Other (OTH) AF: 0.515 AC: 31121 AN: 60380

GnomAD4 genome AF: 0.515 AC: 78209 AN: 151986 Hom.: 20081 Cov.: 32 AF XY: 0.516 AC XY: 38348 AN XY: 74298

African (AFR) AF: 0.521 AC: 21573 AN: 41430

American (AMR) AF: 0.553 AC: 8457 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 1832 AN: 3472

East Asian (EAS) AF: 0.526 AC: 2713 AN: 5160

South Asian (SAS) AF: 0.583 AC: 2814 AN: 4824

European-Finnish (FIN) AF: 0.469 AC: 4955 AN: 10564

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 34048 AN: 67936

Other (OTH) AF: 0.523 AC: 1105 AN: 2112

Alfa AF: 0.469 Hom.: 4855

Bravo AF: 0.521

Asia WGS AF: 0.554 AC: 1925 AN: 3478

EpiCase AF: 0.510

EpiControl AF: 0.518

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Primary ciliary dyskinesia 13 (4)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.034
DANN	Benign	0.44
PhyloP100		-2.5
PromoterAI		0.0038	Neutral
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: rs2288019; hg19: chr16-84209634; COSMIC: COSV58985343; COSMIC: COSV58985343;