rs72655982

Positions:

chr7-21570073-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001277115.2(DNAH11):c.1199C>T(p.Thr400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,597,816 control chromosomes in the GnomAD database, including 1,819 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 139 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1680 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.762

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:

LOC105375183 (HGNC:):

LOC105375183 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-21570073-C-T is Benign according to our data. Variant chr7-21570073-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 163095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21570073-C-T is described in Lovd as [Benign]. Variant chr7-21570073-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0568 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.1199C>T	p.Thr400Ile	missense_variant	7/82	ENST00000409508.8	NP_001264044.1
LOC105375183	XR_007060247.1 linkuse as main transcript	n.282+3253G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.1199C>T	p.Thr400Ile	missense_variant	7/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000496218.1 linkuse as main transcript	n.85C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6217

AN:

152120

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0206

Gnomad ASJ

AF:

0.0421

Gnomad EAS

AF:

0.0201

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0464

Gnomad OTH

AF:

0.0397

GnomAD3 exomes

AF:

0.0395

AC:

9028

AN:

228282

Hom.:

215

AF XY:

0.0413

AC XY:

5102

AN XY:

123640

show subpopulations

Gnomad AFR exome

AF:

0.0379

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0468

Gnomad EAS exome

AF:

0.0241

Gnomad SAS exome

AF:

0.0550

Gnomad FIN exome

AF:

0.0351

Gnomad NFE exome

AF:

0.0467

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0452

AC:

65374

AN:

1445578

Hom.:

1680

Cov.:

AF XY:

0.0456

AC XY:

32710

AN XY:

717892

show subpopulations

Gnomad4 AFR exome

AF:

0.0422

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0447

Gnomad4 EAS exome

AF:

0.0131

Gnomad4 SAS exome

AF:

0.0560

Gnomad4 FIN exome

AF:

0.0374

Gnomad4 NFE exome

AF:

0.0474

Gnomad4 OTH exome

AF:

0.0428

GnomAD4 genome

AF:

0.0408

AC:

6215

AN:

152238

Hom.:

139

Cov.:

AF XY:

0.0403

AC XY:

3001

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.0205

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.0201

Gnomad4 SAS

AF:

0.0626

Gnomad4 FIN

AF:

0.0365

Gnomad4 NFE

AF:

0.0464

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0450

Hom.:

244

Bravo

AF:

0.0384

TwinsUK

AF:

0.0515

AC:

191

ALSPAC

AF:

0.0483

AC:

186

ESP6500AA

AF:

0.0407

AC:

150

ESP6500EA

AF:

0.0441

AC:

360

ExAC

AF:

0.0394

AC:

4748

Asia WGS

AF:

0.0410

AC:

143

AN:

3476

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	Thr400Ile in exon 7 of DNAH11: This variant is not expected to have clinical sig nificance because it has been identified in 4.4% (360/8170) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs72655982). -

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.33

DANN

Benign

0.30

DEOGEN2

Benign

0.11

.;.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.020

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

.;.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.4

.;N;.

REVEL

Benign

0.037

Sift

Benign

0.49

.;T;.

Polyphen

0.0

.;.;B

Vest4

0.037

ClinPred

0.00038

GERP RS

-5.2

Varity_R

0.047

gMVP

0.066

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.28

Position offset: -4

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