7-21884396-A-G

Position:

chr7-21884396-A-G

Variant summary

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

The NM_001277115.2(DNAH11):c.12493A>G(p.Met4165Val) variant causes a missense change. The variant allele was found at a frequency of 0.802 in 1,608,656 control chromosomes in the GnomAD database, including 528,502 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 39739 hom., cov: 32)

Exomes 𝑓: 0.81 ( 488763 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.69

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=8.890553E-7).

BP6

Variant 7-21884396-A-G is Benign according to our data. Variant chr7-21884396-A-G is described in ClinVar as [Benign]. Clinvar id is 178735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21884396-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.832 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.12493A>G	p.Met4165Val	missense_variant	76/82	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.12493A>G	p.Met4165Val	missense_variant	76/82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.695

AC:

105726

AN:

152060

Hom.:

39737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.399

Gnomad AMI

AF:

0.903

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.819

Gnomad EAS

AF:

0.663

Gnomad SAS

AF:

0.743

Gnomad FIN

AF:

0.874

Gnomad MID

AF:

0.778

Gnomad NFE

AF:

0.837

Gnomad OTH

AF:

0.728

GnomAD3 exomes

AF:

0.756

AC:

185702

AN:

245538

Hom.:

72568

AF XY:

0.769

AC XY:

102429

AN XY:

133148

show subpopulations

Gnomad AFR exome

AF:

0.392

Gnomad AMR exome

AF:

0.596

Gnomad ASJ exome

AF:

0.828

Gnomad EAS exome

AF:

0.685

Gnomad SAS exome

AF:

0.745

Gnomad FIN exome

AF:

0.862

Gnomad NFE exome

AF:

0.840

Gnomad OTH exome

AF:

0.787

GnomAD4 exome

AF:

0.814

AC:

1185018

AN:

1456478

Hom.:

488763

Cov.:

AF XY:

0.813

AC XY:

589095

AN XY:

724356

show subpopulations

Gnomad4 AFR exome

AF:

0.379

Gnomad4 AMR exome

AF:

0.608

Gnomad4 ASJ exome

AF:

0.828

Gnomad4 EAS exome

AF:

0.608

Gnomad4 SAS exome

AF:

0.749

Gnomad4 FIN exome

AF:

0.863

Gnomad4 NFE exome

AF:

0.846

Gnomad4 OTH exome

AF:

0.793

GnomAD4 genome

AF:

0.695

AC:

105751

AN:

152178

Hom.:

39739

Cov.:

AF XY:

0.696

AC XY:

51762

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.399

Gnomad4 AMR

AF:

0.689

Gnomad4 ASJ

AF:

0.819

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.743

Gnomad4 FIN

AF:

0.874

Gnomad4 NFE

AF:

0.837

Gnomad4 OTH

AF:

0.728

Alfa

AF:

0.779

Hom.:

22253

Bravo

AF:

0.666

TwinsUK

AF:

0.854

AC:

3168

ALSPAC

AF:

0.848

AC:

3270

ESP6500AA

AF:

0.440

AC:

1752

ESP6500EA

AF:

0.848

AC:

7150

ExAC

AF:

0.755

AC:

91244

Asia WGS

AF:

0.673

AC:

2342

AN:

3478

EpiCase

AF:

0.841

EpiControl

AF:

0.839

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	Met4165Val in exon 76 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 44.0% (1752/3986) of African Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs6461613). -
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	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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

0.096

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

.;.;T

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

T;T;T

MetaRNN

Benign

8.9e-7

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

.;N;.

REVEL

Benign

0.11

Sift

Benign

0.14

.;T;.

Vest4

0.11

ClinPred

0.027

GERP RS

5.7

Varity_R

0.65

gMVP

0.37

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