rs10224537

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.3112A>G(p.Thr1038Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 1,613,570 control chromosomes in the GnomAD database, including 543,034 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48351 hom., cov: 30)

Exomes 𝑓: 0.82 ( 494683 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.361

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=7.558386E-7).

BP6

Variant 7-21600787-A-G is Benign according to our data. Variant chr7-21600787-A-G is described in ClinVar as [Benign]. Clinvar id is 163100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21600787-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 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.3112A>G	p.Thr1038Ala	missense_variant	16/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.3112A>G	p.Thr1038Ala	missense_variant	16/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes

AF:

0.796

AC:

120916

AN:

151858

Hom.:

48310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.857

Gnomad AMR

AF:

0.723

Gnomad ASJ

AF:

0.740

Gnomad EAS

AF:

0.820

Gnomad SAS

AF:

0.717

Gnomad FIN

AF:

0.821

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.842

Gnomad OTH

AF:

0.796

GnomAD3 exomes

AF:

0.782

AC:

194303

AN:

248324

Hom.:

76668

AF XY:

0.784

AC XY:

105519

AN XY:

134644

show subpopulations

Gnomad AFR exome

AF:

0.745

Gnomad AMR exome

AF:

0.655

Gnomad ASJ exome

AF:

0.735

Gnomad EAS exome

AF:

0.811

Gnomad SAS exome

AF:

0.702

Gnomad FIN exome

AF:

0.827

Gnomad NFE exome

AF:

0.839

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.821

AC:

1200035

AN:

1461594

Hom.:

494683

Cov.:

AF XY:

0.818

AC XY:

594577

AN XY:

727086

show subpopulations

Gnomad4 AFR exome

AF:

0.738

Gnomad4 AMR exome

AF:

0.665

Gnomad4 ASJ exome

AF:

0.735

Gnomad4 EAS exome

AF:

0.790

Gnomad4 SAS exome

AF:

0.707

Gnomad4 FIN exome

AF:

0.833

Gnomad4 NFE exome

AF:

0.842

Gnomad4 OTH exome

AF:

0.815

GnomAD4 genome

AF:

0.796

AC:

121007

AN:

151976

Hom.:

48351

Cov.:

AF XY:

0.790

AC XY:

58717

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.752

Gnomad4 AMR

AF:

0.722

Gnomad4 ASJ

AF:

0.740

Gnomad4 EAS

AF:

0.820

Gnomad4 SAS

AF:

0.716

Gnomad4 FIN

AF:

0.821

Gnomad4 NFE

AF:

0.842

Gnomad4 OTH

AF:

0.799

Alfa

AF:

0.824

Hom.:

126620

Bravo

AF:

0.788

TwinsUK

AF:

0.847

AC:

3142

ALSPAC

AF:

0.849

AC:

3272

ESP6500AA

AF:

0.768

AC:

3046

ESP6500EA

AF:

0.838

AC:

6987

ExAC

AF:

0.788

AC:

95266

Asia WGS

AF:

0.810

AC:

2820

AN:

3478

EpiCase

AF:

0.835

EpiControl

AF:

0.830

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Thr1038Ala in exon 16 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 23.2% (920/3966) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs10224537). -
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, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

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

Dec 19, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

8.7

DANN

Benign

0.89

DEOGEN2

Benign

0.014

.;.;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.047

T;T;T

MetaRNN

Benign

7.6e-7

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.9

.;.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

1.2

.;N;.

REVEL

Benign

0.019

Sift

Benign

0.44

.;T;.

Polyphen

0.0

.;.;B

Vest4

0.018

ClinPred

0.0011

GERP RS

3.6

Varity_R

0.044

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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