chr8-132638081-G-A

Variant names:

• chr8-132638081-G-A
• rs74599901
• NM_012472.6:c.283C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001321963.2(DNAAF11):​c.-78C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,613,878 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (154 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (116 hom.)
• Consequence: DNAAF11 NM_001321963.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.34
• Publications: 2 publications found

Genes affected

DNAAF11 (HGNC:16725): (dynein axonemal assembly factor 11) The protein encoded by this gene contains several leucine-rich repeat domains and appears to be involved in the motility of cilia. Defects in this gene are a cause of primary ciliary dyskinesia-19 (CILD19). Alternative splicing of this gene results in multiple transcript variants. Related pseudogenes have been identified on chromosomes 4, 11 and 22. [provided by RefSeq, Apr 2016]

DNAAF11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 19

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 8-132638081-G-A is Benign according to our data. Variant chr8-132638081-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321963.2. 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
	DNAAF11	NM_012472.6	MANE Select	c.283C>T	p.Leu95Leu	synonymous	Exon 4 of 12	NP_036604.2
	DNAAF11	NM_001321963.2		c.-78C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001308892.1
	DNAAF11	NM_001321964.2		c.-78C>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001308893.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAAF11	ENST00000620350.5	TSL:1 MANE Select	c.283C>T	p.Leu95Leu	synonymous	Exon 4 of 12	ENSP00000484634.1
	DNAAF11	ENST00000519595.5	TSL:1	c.283C>T	p.Leu95Leu	synonymous	Exon 4 of 12	ENSP00000429791.1
	DNAAF11	ENST00000250173.5	TSL:1	c.283C>T	p.Leu95Leu	synonymous	Exon 4 of 13	ENSP00000250173.2

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3398 AN: 152136 Hom.: 150 Cov.: 32

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00930

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: 0.000221

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00575 AC: 1443 AN: 250898 AF XY: 0.00417

Gnomad AFR exome AF: 0.0784

Gnomad AMR exome AF: 0.00365

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00231 AC: 3372 AN: 1461624 Hom.: 116 Cov.: 31 AF XY: 0.00201 AC XY: 1461 AN XY: 727092

African (AFR) AF: 0.0803 AC: 2687 AN: 33474

American (AMR) AF: 0.00456 AC: 204 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39684

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5768

European-Non Finnish (NFE) AF: 0.0000854 AC: 95 AN: 1111932

Other (OTH) AF: 0.00581 AC: 351 AN: 60390

GnomAD4 genome AF: 0.0224 AC: 3413 AN: 152254 Hom.: 154 Cov.: 32 AF XY: 0.0215 AC XY: 1602 AN XY: 74434

African (AFR) AF: 0.0775 AC: 3217 AN: 41530

American (AMR) AF: 0.00928 AC: 142 AN: 15296

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: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68018

Other (OTH) AF: 0.0185 AC: 39 AN: 2108

Alfa AF: 0.00986 Hom.: 39

Bravo AF: 0.0253

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia 19 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	1.0
DANN	Benign	0.69
PhyloP100		1.3
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: rs74599901; hg19: chr8-133650327;