rs2214326

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.10399G>A(p.Ala3467Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 1,611,438 control chromosomes in the GnomAD database, including 114,914 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3467S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.39 ( 12169 hom., cov: 31)

Exomes 𝑓: 0.36 ( 102745 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.144

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=2.241899E-6).

BP6

Variant 7-21816533-G-A is Benign according to our data. Variant chr7-21816533-G-A is described in ClinVar as [Benign]. Clinvar id is 178732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21816533-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 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.10399G>A	p.Ala3467Thr	missense_variant	64/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.10399G>A	p.Ala3467Thr	missense_variant	64/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58785

AN:

151738

Hom.:

12156

Cov.:

show subpopulations

Gnomad AFR

AF:

0.392

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.818

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.363

Gnomad MID

AF:

0.421

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.389

GnomAD3 exomes

AF:

0.420

AC:

103281

AN:

246088

Hom.:

23940

AF XY:

0.412

AC XY:

54947

AN XY:

133412

show subpopulations

Gnomad AFR exome

AF:

0.390

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.822

Gnomad SAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.361

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.363

AC:

530277

AN:

1459582

Hom.:

102745

Cov.:

AF XY:

0.364

AC XY:

264150

AN XY:

725854

show subpopulations

Gnomad4 AFR exome

AF:

0.395

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.278

Gnomad4 EAS exome

AF:

0.823

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.356

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.378

GnomAD4 genome

AF:

0.387

AC:

58840

AN:

151856

Hom.:

12169

Cov.:

AF XY:

0.395

AC XY:

29310

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.393

Gnomad4 AMR

AF:

0.483

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.818

Gnomad4 SAS

AF:

0.427

Gnomad4 FIN

AF:

0.363

Gnomad4 NFE

AF:

0.338

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.355

Hom.:

24868

Bravo

AF:

0.399

TwinsUK

AF:

0.343

AC:

1270

ALSPAC

AF:

0.357

AC:

1375

ESP6500AA

AF:

0.385

AC:

1532

ESP6500EA

AF:

0.330

AC:

2736

ExAC

AF:

0.409

AC:

49439

Asia WGS

AF:

0.574

AC:

1997

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ala3467Thr in exon 64 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 38.5% (1532/3984) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs2214326). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 18, 2014	- -

Primary ciliary dyskinesia

Benign:2

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

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

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

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.013

DANN

Benign

0.39

DEOGEN2

Benign

0.024

.;.;T

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.073

LIST_S2

Benign

0.54

T;T;T

MetaRNN

Benign

0.0000022

T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

0.83

.;N;.

REVEL

Benign

0.089

Sift

Benign

1.0

.;T;.

Vest4

0.018

ClinPred

0.013

GERP RS

-12

Varity_R

0.055

gMVP

0.096

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