rs5882827

chr7-21867834-G-GT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001277115.2(DNAH11):c.11691-20dup 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 198650.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.11691-20dup		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.11691-20dup		intron_variant		5	NM_001277115.2	P1

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

GnomAD3 exomes AF: 0.600 AC: 96921 AN: 161480 Hom.: 31383 AF XY: 0.604 AC XY: 51498 AN XY: 85224

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 SAS exome AF: 0.495

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

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.507

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.493

Gnomad4 FIN exome AF: 0.701

Gnomad4 NFE exome AF: 0.747

Gnomad4 OTH exome AF: 0.647

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

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.721

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.580

Alfa AF: 0.637 Hom.: 5572

Bravo AF: 0.513

Asia WGS AF: 0.362 AC: 1261 AN: 3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Uncertain:1 Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 29, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 21, 2019	- -

Primary ciliary dyskinesia 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

DNAH11-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 07, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs5882827; hg19: chr7-21907452;