Variant rs2285942 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.54C>T(p.Thr18=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,548,618 control chromosomes in the GnomAD database, including 14,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.099 ( 932 hom., cov: 33)

Exomes 𝑓: 0.14 ( 13870 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.521

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 7-21543299-C-T is Benign according to our data. Variant chr7-21543299-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21543299-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.521 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 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.54C>T	p.Thr18=	synonymous_variant	1/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.54C>T	p.Thr18=	synonymous_variant	1/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0986

AC:

14999

AN:

152088

Hom.:

932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0326

Gnomad AMI

AF:

0.0833

Gnomad AMR

AF:

0.0846

Gnomad ASJ

AF:

0.0766

Gnomad EAS

AF:

0.0561

Gnomad SAS

AF:

0.0589

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.0984

GnomAD3 exomes

AF:

0.100

AC:

15074

AN:

150352

Hom.:

933

AF XY:

0.101

AC XY:

8133

AN XY:

80262

show subpopulations

Gnomad AFR exome

AF:

0.0261

Gnomad AMR exome

AF:

0.0596

Gnomad ASJ exome

AF:

0.0843

Gnomad EAS exome

AF:

0.0439

Gnomad SAS exome

AF:

0.0615

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.144

Gnomad OTH exome

AF:

0.0996

GnomAD4 exome

AF:

0.136

AC:

189940

AN:

1396412

Hom.:

13870

Cov.:

AF XY:

0.134

AC XY:

92020

AN XY:

688484

show subpopulations

Gnomad4 AFR exome

AF:

0.0268

Gnomad4 AMR exome

AF:

0.0664

Gnomad4 ASJ exome

AF:

0.0873

Gnomad4 EAS exome

AF:

0.0779

Gnomad4 SAS exome

AF:

0.0650

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.120

GnomAD4 genome

AF:

0.0985

AC:

14998

AN:

152206

Hom.:

932

Cov.:

AF XY:

0.0955

AC XY:

7108

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0326

Gnomad4 AMR

AF:

0.0844

Gnomad4 ASJ

AF:

0.0766

Gnomad4 EAS

AF:

0.0564

Gnomad4 SAS

AF:

0.0585

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.0974

Alfa

AF:

0.134

Hom.:

2514

Bravo

AF:

0.0917

Asia WGS

AF:

0.0520

AC:

180

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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	Thr18Thr in exon 1 of DNAH11: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 10.9% (715/6530) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2285942). -

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	Invitae	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

3.7

DANN

Benign

0.92

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