rs140048925

Positions:

chr7-21704576-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.6416G>A(p.Arg2139Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000925 in 1,613,728 control chromosomes in the GnomAD database, including 9 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00056 ( 5 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.34

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=0.006824881).

BP6

Variant 7-21704576-G-A is Benign according to our data. Variant chr7-21704576-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 238929.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21704576-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00443 (674/152294) while in subpopulation AFR AF= 0.0144 (598/41552). AF 95% confidence interval is 0.0134. There are 4 homozygotes in gnomad4. There are 325 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.6416G>A	p.Arg2139Lys	missense_variant	38/82	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.6416G>A	p.Arg2139Lys	missense_variant	38/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes

AF:

0.00443

AC:

674

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0144

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00115

AC:

285

AN:

248616

Hom.:

AF XY:

0.000853

AC XY:

115

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.0136

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000799

Gnomad OTH exome

AF:

0.000995

GnomAD4 exome

AF:

0.000560

AC:

819

AN:

1461434

Hom.:

Cov.:

AF XY:

0.000469

AC XY:

341

AN XY:

726986

show subpopulations

Gnomad4 AFR exome

AF:

0.0165

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000104

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00443

AC:

674

AN:

152294

Hom.:

Cov.:

AF XY:

0.00436

AC XY:

325

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0144

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00214

Hom.:

Bravo

AF:

0.00516

ESP6500AA

AF:

0.0115

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00139

AC:

168

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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	Arg2139Lys in exon 38 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 1.1% (46/4016) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs140048925). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 29, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

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

Apr 27, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.020

.;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.62

T;T;T

MetaRNN

Benign

0.0068

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

PrimateAI

Benign

0.32

PROVEAN

Benign

0.010

.;N;.

REVEL

Benign

0.041

Sift

Benign

1.0

.;T;.

Vest4

0.34

MVP

0.27

ClinPred

0.0023

GERP RS

3.2

Varity_R

0.064

gMVP

0.38

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