rs5882827

Variant names:

• chr7-21867834-G-GT
• rs5882827
• NM_001277115.2:c.11691-20dupT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001277115.2(DNAH11):​c.11691-20dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 1,548,976 control chromosomes in the GnomAD database, including 377,222 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.54 (26740 hom., cov: 0)
  • Exomes 𝑓: 0.70 (350482 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.558
• Publications: 3 publications found

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

DNAH11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP6: Variant 7-21867834-G-GT is Benign according to our data. Variant chr7-21867834-G-GT is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 198650.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.11691-20dupT		intron	N/A	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.11691-25_11691-24insT		intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82033 AN: 150502 Hom.: 26744 Cov.: 0

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.585

GnomAD2 exomes AF: 0.600 AC: 96921 AN: 161480 AF XY: 0.604

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.493

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.357

Gnomad FIN exome AF: 0.694

Gnomad NFE exome AF: 0.736

Gnomad OTH exome AF: 0.646

GnomAD4 exome AF: 0.696 AC: 973546 AN: 1398364 Hom.: 350482 Cov.: 34 AF XY: 0.692 AC XY: 477394 AN XY: 690154

African (AFR) AF: 0.163 AC: 5116 AN: 31386

American (AMR) AF: 0.507 AC: 18224 AN: 35970

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 17989 AN: 25176

East Asian (EAS) AF: 0.363 AC: 13085 AN: 36082

South Asian (SAS) AF: 0.493 AC: 39057 AN: 79200

European-Finnish (FIN) AF: 0.701 AC: 34652 AN: 49464

Middle Eastern (MID) AF: 0.606 AC: 3429 AN: 5660

European-Non Finnish (NFE) AF: 0.747 AC: 804501 AN: 1077454

Other (OTH) AF: 0.647 AC: 37493 AN: 57972

GnomAD4 genome AF: 0.545 AC: 82017 AN: 150612 Hom.: 26740 Cov.: 0 AF XY: 0.541 AC XY: 39780 AN XY: 73592

African (AFR) AF: 0.188 AC: 7589 AN: 40380

American (AMR) AF: 0.553 AC: 8413 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2493 AN: 3458

East Asian (EAS) AF: 0.347 AC: 1792 AN: 5160

South Asian (SAS) AF: 0.474 AC: 2275 AN: 4800

European-Finnish (FIN) AF: 0.707 AC: 7414 AN: 10490

Middle Eastern (MID) AF: 0.596 AC: 174 AN: 292

European-Non Finnish (NFE) AF: 0.738 AC: 50012 AN: 67806

Other (OTH) AF: 0.580 AC: 1217 AN: 2098

Alfa AF: 0.637 Hom.: 5572

Bravo AF: 0.513

Asia WGS AF: 0.362 AC: 1261 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)
-	-	1	DNAH11-related disorder (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.56
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: rs5882827; hg19: chr7-21907452;