rs59447021

Positions:

• chr7-21683955-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.5621+11A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,611,360 control chromosomes in the GnomAD database, including 34,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4173 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30811 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-21683955-A-T is Benign according to our data. Variant chr7-21683955-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 93692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21683955-A-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.5621+11A>T		intron_variant		ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.5621+11A>T		intron_variant		5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35108 AN: 151968 Hom.: 4160 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.232

GnomAD3 exomes AF: 0.209 AC: 51733 AN: 247472 Hom.: 5603 AF XY: 0.211 AC XY: 28271 AN XY: 134240

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.213

Gnomad SAS exome AF: 0.220

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.203 AC: 296909 AN: 1459274 Hom.: 30811 Cov.: 33 AF XY: 0.204 AC XY: 148402 AN XY: 725846

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.269

Gnomad4 EAS exome AF: 0.201

Gnomad4 SAS exome AF: 0.211

Gnomad4 FIN exome AF: 0.227

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.231 AC: 35155 AN: 152086 Hom.: 4173 Cov.: 32 AF XY: 0.232 AC XY: 17258 AN XY: 74344

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.235

Alfa AF: 0.224 Hom.: 737

Bravo AF: 0.228

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 11, 2013	- -
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	5621+11A>T in intron 32 of DNAH11: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 28.1% (1039/3698) of African American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs59447021). -

Primary ciliary dyskinesia Benign:2

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

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.016
DANN	Benign	0.53

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: rs59447021; hg19: chr7-21723573; COSMIC: COSV60946253;