rs202113269

Variant names:

• chr16-84165963-C-T
• rs202113269
• NM_178452.6:c.1030+14C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-84165963-C-T
• chr16-84165963-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001318756.1(DNAAF1):​c.288C>T​(p.Ala96Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,610,782 control chromosomes in the GnomAD database, including 75 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0019 (71 hom.)
• Consequence: DNAAF1 NM_001318756.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.202
• Publications: 1 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=-0.9).
• BP6: Variant 16-84165963-C-T is Benign according to our data. Variant chr16-84165963-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.202 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00119 (179/150896) while in subpopulation SAS AF = 0.0341 (163/4784). AF 95% confidence interval is 0.0298. There are 4 homozygotes in GnomAd4. There are 134 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001318756.1. 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.1030+14C>T		intron	N/A	NP_848547.4
	DNAAF1	NM_001318756.1		c.288C>T	p.Ala96Ala	synonymous	Exon 3 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.1030+14C>T		intron	N/A	ENSP00000367815.5	Q8NEP3-1
	DNAAF1	ENST00000963696.1		c.1044C>T	p.Ala348Ala	synonymous	Exon 7 of 12	ENSP00000633755.1
	DNAAF1	ENST00000963697.1		c.1030+14C>T		intron	N/A	ENSP00000633756.1

Frequencies

GnomAD3 genomes AF: 0.00121 AC: 183 AN: 150818 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.000123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0348

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00325

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000967

GnomAD2 exomes AF: 0.00371 AC: 931 AN: 251220 AF XY: 0.00492

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00194 AC: 2838 AN: 1459886 Hom.: 71 Cov.: 33 AF XY: 0.00278 AC XY: 2022 AN XY: 726258

African (AFR) AF: 0.000151 AC: 5 AN: 33212

American (AMR) AF: 0.0000895 AC: 4 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39642

South Asian (SAS) AF: 0.0303 AC: 2612 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53310

Middle Eastern (MID) AF: 0.00209 AC: 11 AN: 5260

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111228

Other (OTH) AF: 0.00226 AC: 136 AN: 60230

GnomAD4 genome AF: 0.00119 AC: 179 AN: 150896 Hom.: 4 Cov.: 31 AF XY: 0.00182 AC XY: 134 AN XY: 73584

African (AFR) AF: 0.000122 AC: 5 AN: 40890

American (AMR) AF: 0.00 AC: 0 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5148

South Asian (SAS) AF: 0.0341 AC: 163 AN: 4784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10262

Middle Eastern (MID) AF: 0.00352 AC: 1 AN: 284

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67924

Other (OTH) AF: 0.000959 AC: 2 AN: 2086

Alfa AF: 0.000370 Hom.: 0

Bravo AF: 0.000253

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 13 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.31
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism

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: rs202113269; hg19: chr16-84199569; COSMIC: COSV100533635;