chr7-21543303-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001277115.2(DNAH11):c.58C>A(p.Arg20Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000973 in 1,549,134 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00088 ( 14 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -0.343

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040258765).

BP6

Variant 7-21543303-C-A is Benign according to our data. Variant chr7-21543303-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 218583.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=3, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00187 (285/152310) while in subpopulation AMR AF= 0.0161 (247/15308). AF 95% confidence interval is 0.0145. There are 4 homozygotes in gnomad4. There are 176 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 1 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.58C>A	p.Arg20Ser	missense_variant	Exon 1 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000607050.1 link	n.-143C>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00187

AC:

285

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000970

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00549

AC:

826

AN:

150532

Hom.:

AF XY:

0.00408

AC XY:

328

AN XY:

80354

show subpopulations

Gnomad AFR exome

AF:

0.000278

Gnomad AMR exome

AF:

0.0318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00242

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000694

Gnomad OTH exome

AF:

0.00304

GnomAD4 exome

AF:

0.000876

AC:

1223

AN:

1396824

Hom.:

Cov.:

AF XY:

0.000757

AC XY:

521

AN XY:

688692

show subpopulations

Gnomad4 AFR exome

AF:

0.000190

Gnomad4 AMR exome

AF:

0.0290

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00328

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000167

Gnomad4 OTH exome

AF:

0.000829

GnomAD4 genome

AF:

0.00187

AC:

285

AN:

152310

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.0161

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000972

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000698

Hom.:

Bravo

AF:

0.00331

ExAC

AF:

0.000451

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:2

Jun 16, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Arg20Ser in exon 1 of DNAH11: This variant is not expected to have clinical sign ificance because it has been identified in 3.8% (5/132) of Mexican chromosomes f rom a broad population by the 1000 Genomes Project (http://www.ncbi.nlm.nih.gov/ projects/SNP; dbSNP rs72655967). -

not provided

Benign:2

Feb 29, 2024

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

See Variant Classification Assertion Criteria. -

Feb 16, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.42

T;T;T

MetaRNN

Benign

0.0040

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;.;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

.;N;.

REVEL

Benign

0.11

Sift

Benign

0.095

.;T;.

Polyphen

0.093

.;.;B

Vest4

0.20

MVP

0.085

ClinPred

0.017

GERP RS

-0.63

Varity_R

0.36

gMVP

0.43

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