rs55666134

Positions:

• chr7-21683813-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.5490G>A​(p.Leu1830Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,610,424 control chromosomes in the GnomAD database, including 17,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16065 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.377

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-21683813-G-A is Benign according to our data. Variant chr7-21683813-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 93691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21683813-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.5490G>A	p.Leu1830Leu	synonymous_variant	32/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.5490G>A	p.Leu1830Leu	synonymous_variant	32/82	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17819 AN: 152060 Hom.: 1230 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.129 AC: 31967 AN: 247102 Hom.: 2277 AF XY: 0.132 AC XY: 17762 AN XY: 134064

Gnomad AFR exome AF: 0.0372

Gnomad AMR exome AF: 0.0725

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.107

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.145 AC: 211014 AN: 1458246 Hom.: 16065 Cov.: 31 AF XY: 0.144 AC XY: 104462 AN XY: 725222

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.0764

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.153

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.117 AC: 17820 AN: 152178 Hom.: 1229 Cov.: 32 AF XY: 0.117 AC XY: 8688 AN XY: 74388

Gnomad4 AFR AF: 0.0420

Gnomad4 AMR AF: 0.101

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.118

Alfa AF: 0.146 Hom.: 2592

Bravo AF: 0.109

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Leu1830Leu in exon 32 of DNAH11: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 15.0% (1240/8258) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs55666134). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 05, 2013	- -

Primary ciliary dyskinesia Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 29, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.0
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs55666134; hg19: chr7-21723431; COSMIC: COSV60957464;