rs2285944

Positions:

chr7-21543346-A-T

Variant summary

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

The NM_001277115.2(DNAH11):c.101A>T(p.Glu34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,550,724 control chromosomes in the GnomAD database, including 181,836 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 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. E34L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.45 ( 15491 hom., cov: 34)

Exomes 𝑓: 0.48 ( 166345 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.369

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=3.2663345E-4).

BP6

Variant 7-21543346-A-T is Benign according to our data. Variant chr7-21543346-A-T is described in ClinVar as [Benign]. Clinvar id is 93683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21543346-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 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.101A>T	p.Glu34Val	missense_variant	1/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.101A>T	p.Glu34Val	missense_variant	1/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67793

AN:

151720

Hom.:

15472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.323

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.482

Gnomad EAS

AF:

0.260

Gnomad SAS

AF:

0.493

Gnomad FIN

AF:

0.414

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.465

GnomAD3 exomes

AF:

0.437

AC:

66886

AN:

152884

Hom.:

15340

AF XY:

0.449

AC XY:

36502

AN XY:

81260

show subpopulations

Gnomad AFR exome

AF:

0.432

Gnomad AMR exome

AF:

0.307

Gnomad ASJ exome

AF:

0.494

Gnomad EAS exome

AF:

0.250

Gnomad SAS exome

AF:

0.508

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.494

Gnomad OTH exome

AF:

0.448

GnomAD4 exome

AF:

0.485

AC:

678031

AN:

1398886

Hom.:

166345

Cov.:

AF XY:

0.486

AC XY:

335054

AN XY:

689954

show subpopulations

Gnomad4 AFR exome

AF:

0.429

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.493

Gnomad4 EAS exome

AF:

0.300

Gnomad4 SAS exome

AF:

0.509

Gnomad4 FIN exome

AF:

0.430

Gnomad4 NFE exome

AF:

0.499

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.447

AC:

67846

AN:

151838

Hom.:

15491

Cov.:

AF XY:

0.442

AC XY:

32813

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.363

Gnomad4 ASJ

AF:

0.482

Gnomad4 EAS

AF:

0.261

Gnomad4 SAS

AF:

0.495

Gnomad4 FIN

AF:

0.414

Gnomad4 NFE

AF:

0.494

Gnomad4 OTH

AF:

0.461

Alfa

AF:

0.482

Hom.:

5716

Bravo

AF:

0.441

TwinsUK

AF:

0.495

AC:

1835

ALSPAC

AF:

0.491

AC:

1892

ESP6500AA

AF:

0.380

AC:

1320

ESP6500EA

AF:

0.451

AC:

3331

ExAC

AF:

0.325

AC:

18950

Asia WGS

AF:

0.334

AC:

1161

AN:

3478

ClinVar

Significance: 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	Eurofins Ntd Llc (ga)	Oct 28, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Glu34Val in exon 1 of DNAH11: This variant is not expected to have clinical sign ificance because it has been identified in 45.1% (3331/7390) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs2285944). -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

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

0.11

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.029

.;.;T

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.61

T;T;T

MetaRNN

Benign

0.00033

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

.;.;L

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

.;N;.

REVEL

Benign

0.081

Sift

Uncertain

0.027

.;D;.

Polyphen

0.86

.;.;P

Vest4

0.12

ClinPred

0.0083

GERP RS

2.3

Varity_R

0.39

gMVP

0.57

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