chr7-21861922-T-C

Position:

chr7-21861922-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.11272T>C(p.Ser3758Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,613,584 control chromosomes in the GnomAD database, including 2,572 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 1012 hom., cov: 32)

Exomes 𝑓: 0.033 ( 1560 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.223

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:

DNAH11 (HGNC:):

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=0.0031466782).

BP6

Variant 7-21861922-T-C is Benign according to our data. Variant chr7-21861922-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 163125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21861922-T-C is described in Lovd as [Benign]. Variant chr7-21861922-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 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.11272T>C	p.Ser3758Pro	missense_variant	69/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.11272T>C	p.Ser3758Pro	missense_variant	69/82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 linkuse as main transcript	n.455T>C		non_coding_transcript_exon_variant	4/4	4
DNAH11	ENST00000607413.5 linkuse as main transcript	n.535T>C		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.0809

AC:

12296

AN:

152012

Hom.:

1009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.0573

Gnomad AMR

AF:

0.0432

Gnomad ASJ

AF:

0.0521

Gnomad EAS

AF:

0.00348

Gnomad SAS

AF:

0.0360

Gnomad FIN

AF:

0.0209

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0291

Gnomad OTH

AF:

0.0724

GnomAD3 exomes

AF:

0.0393

AC:

9763

AN:

248662

Hom.:

501

AF XY:

0.0374

AC XY:

5040

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.0460

Gnomad EAS exome

AF:

0.00212

Gnomad SAS exome

AF:

0.0374

Gnomad FIN exome

AF:

0.0217

Gnomad NFE exome

AF:

0.0277

Gnomad OTH exome

AF:

0.0387

GnomAD4 exome

AF:

0.0333

AC:

48707

AN:

1461454

Hom.:

1560

Cov.:

AF XY:

0.0332

AC XY:

24137

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.0266

Gnomad4 ASJ exome

AF:

0.0440

Gnomad4 EAS exome

AF:

0.00134

Gnomad4 SAS exome

AF:

0.0402

Gnomad4 FIN exome

AF:

0.0206

Gnomad4 NFE exome

AF:

0.0281

Gnomad4 OTH exome

AF:

0.0436

GnomAD4 genome

AF:

0.0810

AC:

12315

AN:

152130

Hom.:

1012

Cov.:

AF XY:

0.0799

AC XY:

5945

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.214

Gnomad4 AMR

AF:

0.0430

Gnomad4 ASJ

AF:

0.0521

Gnomad4 EAS

AF:

0.00349

Gnomad4 SAS

AF:

0.0357

Gnomad4 FIN

AF:

0.0209

Gnomad4 NFE

AF:

0.0291

Gnomad4 OTH

AF:

0.0726

Alfa

AF:

0.0400

Hom.:

561

Bravo

AF:

0.0895

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0293

AC:

113

ESP6500AA

AF:

0.202

AC:

833

ESP6500EA

AF:

0.0281

AC:

237

ExAC

AF:

0.0418

AC:

5054

Asia WGS

AF:

0.0530

AC:

182

AN:

3478

EpiCase

AF:

0.0289

EpiControl

AF:

0.0318

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ser3758Pro in exon 69 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 20.2% (833/4116) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs17145720). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 17, 2018	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.18

.;.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.57

T;T;T

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.3

.;N;.

REVEL

Benign

0.23

Sift

Benign

0.27

.;T;.

Vest4

0.16

ClinPred

0.024

GERP RS

5.7

Varity_R

0.31

gMVP

0.65

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