chr7-21600743-T-C

Position:

chr7-21600743-T-C

Variant summary

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

The NM_001277115.2(DNAH11):c.3068T>C(p.Val1023Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,613,428 control chromosomes in the GnomAD database, including 136,336 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 10179 hom., cov: 31)

Exomes 𝑓: 0.41 ( 126157 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.927

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=0.002362281).

BP6

Variant 7-21600743-T-C is Benign according to our data. Variant chr7-21600743-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 178725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21600743-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 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.3068T>C	p.Val1023Ala	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.3068T>C	p.Val1023Ala	missense_variant	16/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51479

AN:

151782

Hom.:

10176

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.590

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.0203

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.466

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.351

GnomAD3 exomes

AF:

0.354

AC:

88106

AN:

248644

Hom.:

17669

AF XY:

0.356

AC XY:

47985

AN XY:

134838

show subpopulations

Gnomad AFR exome

AF:

0.164

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.402

Gnomad EAS exome

AF:

0.0125

Gnomad SAS exome

AF:

0.261

Gnomad FIN exome

AF:

0.464

Gnomad NFE exome

AF:

0.442

Gnomad OTH exome

AF:

0.400

GnomAD4 exome

AF:

0.405

AC:

592415

AN:

1461528

Hom.:

126157

Cov.:

AF XY:

0.403

AC XY:

292987

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.325

Gnomad4 ASJ exome

AF:

0.403

Gnomad4 EAS exome

AF:

0.0267

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.468

Gnomad4 NFE exome

AF:

0.439

Gnomad4 OTH exome

AF:

0.381

GnomAD4 genome

AF:

0.339

AC:

51493

AN:

151900

Hom.:

10179

Cov.:

AF XY:

0.334

AC XY:

24814

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.331

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.0203

Gnomad4 SAS

AF:

0.249

Gnomad4 FIN

AF:

0.466

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.353

Alfa

AF:

0.411

Hom.:

33982

Bravo

AF:

0.323

TwinsUK

AF:

0.425

AC:

1577

ALSPAC

AF:

0.447

AC:

1722

ESP6500AA

AF:

0.178

AC:

703

ESP6500EA

AF:

0.434

AC:

3630

ExAC

AF:

0.352

AC:

42605

Asia WGS

AF:

0.195

AC:

678

AN:

3478

EpiCase

AF:

0.441

EpiControl

AF:

0.435

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

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	Val1023Ala in exon 16 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 43.4% (3630/8356) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs10269582). -

Primary ciliary dyskinesia

Benign:2

Likely 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	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 21, 2019	This variant is associated with the following publications: (PMID: 12142464) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Primary ciliary dyskinesia 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.21

DEOGEN2

Benign

0.056

.;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.53

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

.;.;L

MutationTaster

Benign

0.085

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.7

.;N;.

REVEL

Benign

0.061

Sift

Benign

1.0

.;T;.

Polyphen

0.029

.;.;B

Vest4

0.055

ClinPred

0.0070

GERP RS

4.5

Varity_R

0.058

gMVP

0.40

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