rs57208694

Positions:

Variant summary

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

The NM_001277115.2(DNAH11):c.4377+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,607,068 control chromosomes in the GnomAD database, including 186,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19942 hom., cov: 31)

Exomes 𝑓: 0.47 ( 166266 hom. )

Consequence

DNAH11
NM_001277115.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.43

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=-0.89).

BP6

Variant 7-21619237-A-G is Benign according to our data. Variant chr7-21619237-A-G is described in ClinVar as [Benign]. Clinvar id is 93687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21619237-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.4377+15A>G		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.4377+15A>G		intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000465593.1 linkuse as main transcript	n.403+15A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.503

AC:

76339

AN:

151830

Hom.:

19917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.595

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.439

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.799

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.417

Gnomad MID

AF:

0.331

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.475

GnomAD3 exomes

AF:

0.473

AC:

114285

AN:

241688

Hom.:

28194

AF XY:

0.473

AC XY:

62013

AN XY:

130992

show subpopulations

Gnomad AFR exome

AF:

0.591

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.396

Gnomad EAS exome

AF:

0.801

Gnomad SAS exome

AF:

0.455

Gnomad FIN exome

AF:

0.424

Gnomad NFE exome

AF:

0.460

Gnomad OTH exome

AF:

0.443

GnomAD4 exome

AF:

0.474

AC:

690272

AN:

1455120

Hom.:

166266

Cov.:

AF XY:

0.473

AC XY:

341937

AN XY:

723220

show subpopulations

Gnomad4 AFR exome

AF:

0.589

Gnomad4 AMR exome

AF:

0.375

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.763

Gnomad4 SAS exome

AF:

0.455

Gnomad4 FIN exome

AF:

0.428

Gnomad4 NFE exome

AF:

0.470

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.503

AC:

76412

AN:

151948

Hom.:

19942

Cov.:

AF XY:

0.500

AC XY:

37151

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.595

Gnomad4 AMR

AF:

0.438

Gnomad4 ASJ

AF:

0.382

Gnomad4 EAS

AF:

0.798

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.417

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.475

Alfa

AF:

0.469

Hom.:

3182

Bravo

AF:

0.509

Asia WGS

AF:

0.618

AC:

2152

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	4377+15A>G in intron 24 of DNAH11: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 47.2% (3899/8262) of European American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS; dbSNP rs57208694). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.5

DANN

Benign

0.33

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