rs72658825

Positions:

chr7-21894893-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001277115.2(DNAH11):c.12943G>A(p.Ala4315Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 1,613,862 control chromosomes in the GnomAD database, including 1,006 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 60 hom., cov: 33)

Exomes 𝑓: 0.033 ( 946 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.720

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 (MetaRNN=0.0017455816).

BP6

Variant 7-21894893-G-A is Benign according to our data. Variant chr7-21894893-G-A is described in ClinVar as [Benign]. Clinvar id is 178738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21894893-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0231 (3516/152254) while in subpopulation NFE AF= 0.0364 (2477/68020). AF 95% confidence interval is 0.0352. There are 60 homozygotes in gnomad4. There are 1635 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.12943G>A	p.Ala4315Thr	missense_variant	79/82	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.12943G>A	p.Ala4315Thr	missense_variant	79/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000479878.1 linkuse as main transcript	n.314G>A		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes

AF:

0.0231

AC:

3519

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00688

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0213

Gnomad ASJ

AF:

0.0389

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0364

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0239

AC:

5963

AN:

249198

Hom.:

107

AF XY:

0.0252

AC XY:

3409

AN XY:

135188

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0349

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0186

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.0358

Gnomad OTH exome

AF:

0.0319

GnomAD4 exome

AF:

0.0332

AC:

48506

AN:

1461608

Hom.:

946

Cov.:

AF XY:

0.0328

AC XY:

23866

AN XY:

727082

show subpopulations

Gnomad4 AFR exome

AF:

0.00547

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0352

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0195

Gnomad4 FIN exome

AF:

0.0148

Gnomad4 NFE exome

AF:

0.0382

Gnomad4 OTH exome

AF:

0.0284

GnomAD4 genome

AF:

0.0231

AC:

3516

AN:

152254

Hom.:

Cov.:

AF XY:

0.0220

AC XY:

1635

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00686

Gnomad4 AMR

AF:

0.0212

Gnomad4 ASJ

AF:

0.0389

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0201

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.0364

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0338

Hom.:

142

Bravo

AF:

0.0234

TwinsUK

AF:

0.0378

AC:

140

ALSPAC

AF:

0.0462

AC:

178

ESP6500AA

AF:

0.00654

AC:

ESP6500EA

AF:

0.0356

AC:

294

ExAC

AF:

0.0238

AC:

2883

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0338

EpiControl

AF:

0.0365

ClinVar

Significance: Benign

Submissions summary: Benign:4

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	Ala4315Thr in exon 79 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 3.6% (294/8262) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs72658825). -

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

Mar 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

DANN

Benign

0.085

DEOGEN2

Benign

0.021

.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.77

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

2.5

.;N;.

REVEL

Benign

0.018

Sift

Benign

1.0

.;T;.

Vest4

0.037

ClinPred

0.00087

GERP RS

2.0

Varity_R

0.040

gMVP

0.11

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