rs59447021

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.28

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.5621+11A>T		intron_variant		ENST00000409508.8

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35108

AN:

151968

Hom.:

4160

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.204

AC XY:

148402

AN XY:

725846

show subpopulations

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.:

AF XY:

0.232

AC XY:

17258

AN XY:

74344

show subpopulations

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:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Eurofins Ntd Llc (ga)	Apr 11, 2013	- -
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

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

not provided

Benign:1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over