rs72655988

Positions:

Variant summary

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

The NM_001277115.2(DNAH11):c.1702G>A(p.Ala568Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0442 in 1,603,644 control chromosomes in the GnomAD database, including 1,805 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 134 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1671 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.48

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 (MetaRNN=0.0040915906).

BP6

Variant 7-21582013-G-A is Benign according to our data. Variant chr7-21582013-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21582013-G-A is described in Lovd as [Benign]. Variant chr7-21582013-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0562 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.1702G>A	p.Ala568Thr	missense_variant	9/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.1702G>A	p.Ala568Thr	missense_variant	9/82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6171

AN:

152154

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0408

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0187

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0364

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0459

Gnomad OTH

AF:

0.0398

GnomAD3 exomes

AF:

0.0395

AC:

9788

AN:

247902

Hom.:

245

AF XY:

0.0411

AC XY:

5527

AN XY:

134464

show subpopulations

Gnomad AFR exome

AF:

0.0390

Gnomad AMR exome

AF:

0.0121

Gnomad ASJ exome

AF:

0.0462

Gnomad EAS exome

AF:

0.0236

Gnomad SAS exome

AF:

0.0541

Gnomad FIN exome

AF:

0.0350

Gnomad NFE exome

AF:

0.0469

Gnomad OTH exome

AF:

0.0376

GnomAD4 exome

AF:

0.0446

AC:

64676

AN:

1451372

Hom.:

1671

Cov.:

AF XY:

0.0450

AC XY:

32494

AN XY:

722518

show subpopulations

Gnomad4 AFR exome

AF:

0.0415

Gnomad4 AMR exome

AF:

0.0135

Gnomad4 ASJ exome

AF:

0.0445

Gnomad4 EAS exome

AF:

0.0126

Gnomad4 SAS exome

AF:

0.0550

Gnomad4 FIN exome

AF:

0.0374

Gnomad4 NFE exome

AF:

0.0468

Gnomad4 OTH exome

AF:

0.0424

GnomAD4 genome

AF:

0.0405

AC:

6169

AN:

152272

Hom.:

134

Cov.:

AF XY:

0.0399

AC XY:

2974

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0406

Gnomad4 AMR

AF:

0.0203

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.0187

Gnomad4 SAS

AF:

0.0620

Gnomad4 FIN

AF:

0.0364

Gnomad4 NFE

AF:

0.0459

Gnomad4 OTH

AF:

0.0394

Alfa

AF:

0.0418

Hom.:

197

Bravo

AF:

0.0381

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0485

AC:

187

ESP6500AA

AF:

0.0401

AC:

145

ESP6500EA

AF:

0.0444

AC:

362

ExAC

AF:

0.0413

AC:

4984

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

EpiCase

AF:

0.0410

EpiControl

AF:

0.0409

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	Ala568Thr in exon 9 of DNAH11: This variant is not expected to have clinical sig nificance because it has been identified in 4.4% (362/8154) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs72655988). -

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	Dec 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;.;T

Eigen

Benign

0.10

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.82

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;.;M

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.3

.;N;.

REVEL

Benign

0.13

Sift

Benign

0.28

.;T;.

Polyphen

0.031

.;.;B

Vest4

0.12

ClinPred

0.026

GERP RS

5.9

Varity_R

0.30

gMVP

0.23

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