Variant rs729657 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001277115.2(DNAH11):c.8155-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,609,344 control chromosomes in the GnomAD database, including 6,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 338 hom., cov: 33)

Exomes 𝑓: 0.084 ( 5674 hom. )

Consequence

DNAH11
NM_001277115.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.211

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 (BayesDel_noAF=-0.75).

BP6

Variant 7-21744419-C-T is Benign according to our data. Variant chr7-21744419-C-T is described in ClinVar as [Benign]. Clinvar id is 257934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21744419-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 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.8155-19C>T		intron_variant		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.8155-19C>T		intron_variant		5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000605912.1 linkuse as main transcript	c.475-451C>T		intron_variant		3		ENSP00000476068

Frequencies

GnomAD3 genomes

AF:

0.0563

AC:

8567

AN:

152068

Hom.:

336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0159

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0434

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.0684

Gnomad FIN

AF:

0.0644

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0870

Gnomad OTH

AF:

0.0527

GnomAD3 exomes

AF:

0.0652

AC:

16015

AN:

245636

Hom.:

673

AF XY:

0.0675

AC XY:

8988

AN XY:

133104

show subpopulations

Gnomad AFR exome

AF:

0.0149

Gnomad AMR exome

AF:

0.0478

Gnomad ASJ exome

AF:

0.0431

Gnomad EAS exome

AF:

0.00174

Gnomad SAS exome

AF:

0.0763

Gnomad FIN exome

AF:

0.0656

Gnomad NFE exome

AF:

0.0863

Gnomad OTH exome

AF:

0.0681

GnomAD4 exome

AF:

0.0841

AC:

122612

AN:

1457156

Hom.:

5674

Cov.:

AF XY:

0.0838

AC XY:

60693

AN XY:

724598

show subpopulations

Gnomad4 AFR exome

AF:

0.0141

Gnomad4 AMR exome

AF:

0.0481

Gnomad4 ASJ exome

AF:

0.0460

Gnomad4 EAS exome

AF:

0.000933

Gnomad4 SAS exome

AF:

0.0781

Gnomad4 FIN exome

AF:

0.0663

Gnomad4 NFE exome

AF:

0.0934

Gnomad4 OTH exome

AF:

0.0764

GnomAD4 genome

AF:

0.0563

AC:

8569

AN:

152188

Hom.:

338

Cov.:

AF XY:

0.0550

AC XY:

4093

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0158

Gnomad4 AMR

AF:

0.0434

Gnomad4 ASJ

AF:

0.0435

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0682

Gnomad4 FIN

AF:

0.0644

Gnomad4 NFE

AF:

0.0870

Gnomad4 OTH

AF:

0.0522

Alfa

AF:

0.0792

Hom.:

283

Bravo

AF:

0.0524

Asia WGS

AF:

0.0280

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.1

DANN

Benign

0.62

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