rs11768670

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.7335G>A(p.Ser2445=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,607,404 control chromosomes in the GnomAD database, including 40,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S2445S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.20 ( 3233 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37286 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.613

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 7-21725879-G-A is Benign according to our data. Variant chr7-21725879-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21725879-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.613 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 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.7335G>A	p.Ser2445=	synonymous_variant	45/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.7335G>A	p.Ser2445=	synonymous_variant	45/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29924

AN:

151894

Hom.:

3233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.183

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0963

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.195

GnomAD3 exomes

AF:

0.189

AC:

45161

AN:

238888

Hom.:

4745

AF XY:

0.190

AC XY:

24439

AN XY:

128966

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.212

Gnomad EAS exome

AF:

0.0521

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.221

AC:

321286

AN:

1455392

Hom.:

37286

Cov.:

AF XY:

0.218

AC XY:

157476

AN XY:

723162

show subpopulations

Gnomad4 AFR exome

AF:

0.133

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.213

Gnomad4 EAS exome

AF:

0.0704

Gnomad4 SAS exome

AF:

0.105

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.197

AC:

29926

AN:

152012

Hom.:

3233

Cov.:

AF XY:

0.195

AC XY:

14484

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.140

Gnomad4 AMR

AF:

0.183

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.0567

Gnomad4 SAS

AF:

0.0961

Gnomad4 FIN

AF:

0.272

Gnomad4 NFE

AF:

0.240

Gnomad4 OTH

AF:

0.193

Alfa

AF:

0.218

Hom.:

8390

Bravo

AF:

0.189

Asia WGS

AF:

0.0830

AC:

290

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ser2445Ser in exon 45 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 23.6% (1930/8180) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11768670). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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

-0.32

Cadd

Benign

8.3

Dann

Benign

0.75

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