7-21892426-C-T

Position:

chr7-21892426-C-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.12509C>T(p.Thr4170Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,604,288 control chromosomes in the GnomAD database, including 138,328 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11341 hom., cov: 32)

Exomes 𝑓: 0.42 ( 126987 hom. )

Consequence

DNAH11
NM_001277115.2 missense, splice_region

Scores

Splicing: ADA: 0.00001818

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.49

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=0.0017268956).

BP6

Variant 7-21892426-C-T is Benign according to our data. Variant chr7-21892426-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21892426-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 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.12509C>T	p.Thr4170Ile	missense_variant, splice_region_variant	77/82	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.12509C>T	p.Thr4170Ile	missense_variant, splice_region_variant	77/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57426

AN:

151830

Hom.:

11334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.337

Gnomad EAS

AF:

0.463

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.422

Gnomad OTH

AF:

0.373

GnomAD3 exomes

AF:

0.395

AC:

97209

AN:

246194

Hom.:

19929

AF XY:

0.398

AC XY:

53069

AN XY:

133474

show subpopulations

Gnomad AFR exome

AF:

0.275

Gnomad AMR exome

AF:

0.297

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.477

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.476

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.406

GnomAD4 exome

AF:

0.415

AC:

603076

AN:

1452340

Hom.:

126987

Cov.:

AF XY:

0.415

AC XY:

298739

AN XY:

720636

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.301

Gnomad4 ASJ exome

AF:

0.356

Gnomad4 EAS exome

AF:

0.414

Gnomad4 SAS exome

AF:

0.373

Gnomad4 FIN exome

AF:

0.470

Gnomad4 NFE exome

AF:

0.427

Gnomad4 OTH exome

AF:

0.407

GnomAD4 genome

AF:

0.378

AC:

57470

AN:

151948

Hom.:

11341

Cov.:

AF XY:

0.380

AC XY:

28233

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.282

Gnomad4 AMR

AF:

0.350

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.462

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.473

Gnomad4 NFE

AF:

0.422

Gnomad4 OTH

AF:

0.373

Alfa

AF:

0.407

Hom.:

30418

Bravo

AF:

0.363

TwinsUK

AF:

0.429

AC:

1591

ALSPAC

AF:

0.446

AC:

1719

ESP6500AA

AF:

0.271

AC:

1054

ESP6500EA

AF:

0.414

AC:

3433

ExAC

AF:

0.394

AC:

47616

Asia WGS

AF:

0.393

AC:

1369

AN:

3478

EpiCase

AF:

0.415

EpiControl

AF:

0.417

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	Thr4170Ile in exon 77 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 41.4% (3433/8302) of European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs12537531). -
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	-	- -

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	Nov 10, 2018	- -
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

0.068

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.9

DANN

Benign

0.66

DEOGEN2

Benign

0.015

.;.;T

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.079

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

2.2

.;N;.

REVEL

Benign

0.031

Sift

Benign

0.68

.;T;.

Vest4

0.027

ClinPred

0.0038

GERP RS

0.88

Varity_R

0.050

gMVP

0.098

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0040

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