rs7156297

Variant names:

• chr14-49635072-G-A
• rs7156297
• NM_018139.3:c.78C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-49635072-G-A
• chr14-49635072-G-C

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_018139.3(DNAAF2):​c.78C>T​(p.Ala26Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00254 in 1,585,936 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A26A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.013 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (31 hom.)
• Consequence: DNAAF2 NM_018139.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.792
• Publications: 1 publications found

Genes affected

DNAAF2 (HGNC:20188): (dynein axonemal assembly factor 2) This gene encodes a highly conserved protein involved in the preassembly of dynein arm complexes which power cilia. These complexes are found in some cilia and are assembled in the cytoplasm prior to transport for cilia formation. Mutations in this gene have been associated with primary ciliary dyskinesia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

DNAAF2 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 10

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• 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=-0.51).
• BP6: Variant 14-49635072-G-A is Benign according to our data. Variant chr14-49635072-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 221190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.792 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0127 (1942/152362) while in subpopulation AFR AF = 0.0437 (1819/41588). AF 95% confidence interval is 0.0421. There are 39 homozygotes in GnomAd4. There are 939 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 39 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018139.3. 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
	DNAAF2	NM_018139.3	MANE Select	c.78C>T	p.Ala26Ala	synonymous	Exon 1 of 3	NP_060609.2	Q9NVR5-1
	DNAAF2	NM_001083908.2		c.78C>T	p.Ala26Ala	synonymous	Exon 1 of 2	NP_001077377.1	Q9NVR5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF2	ENST00000298292.13	TSL:1 MANE Select	c.78C>T	p.Ala26Ala	synonymous	Exon 1 of 3	ENSP00000298292.8	Q9NVR5-1
	DNAAF2	ENST00000406043.3	TSL:1	c.78C>T	p.Ala26Ala	synonymous	Exon 1 of 2	ENSP00000384862.3	Q9NVR5-2

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1939 AN: 152242 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00451

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00284 AC: 560 AN: 197016 AF XY: 0.00217

Gnomad AFR exome AF: 0.0444

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000274

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.00146 AC: 2090 AN: 1433574 Hom.: 31 Cov.: 34 AF XY: 0.00128 AC XY: 910 AN XY: 710698

African (AFR) AF: 0.0453 AC: 1487 AN: 32790

American (AMR) AF: 0.00260 AC: 106 AN: 40794

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.00 AC: 0 AN: 38032

South Asian (SAS) AF: 0.000219 AC: 18 AN: 82248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50080

Middle Eastern (MID) AF: 0.00662 AC: 38 AN: 5740

European-Non Finnish (NFE) AF: 0.000217 AC: 238 AN: 1098976

Other (OTH) AF: 0.00342 AC: 203 AN: 59284

GnomAD4 genome AF: 0.0127 AC: 1942 AN: 152362 Hom.: 39 Cov.: 32 AF XY: 0.0126 AC XY: 939 AN XY: 74502

African (AFR) AF: 0.0437 AC: 1819 AN: 41588

American (AMR) AF: 0.00451 AC: 69 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68034

Other (OTH) AF: 0.0109 AC: 23 AN: 2116

Alfa AF: 0.00395 Hom.: 2

Bravo AF: 0.0145

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	2	Primary ciliary dyskinesia 10 (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.96
PhyloP100		0.79
PromoterAI		-0.021	Neutral
Mutation Taster		=99/1	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: rs7156297; hg19: chr14-50101790;