rs68023059

Positions:

chr7-21735751-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.7552G>A(p.Val2518Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 1,613,926 control chromosomes in the GnomAD database, including 1,244 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 73 hom., cov: 33)

Exomes 𝑓: 0.037 ( 1171 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.40

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=0.003411591).

BP6

Variant 7-21735751-G-A is Benign according to our data. Variant chr7-21735751-G-A is described in ClinVar as [Benign]. Clinvar id is 163108.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21735751-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0256 (3900/152268) while in subpopulation NFE AF= 0.0412 (2803/68022). AF 95% confidence interval is 0.0399. There are 73 homozygotes in gnomad4. There are 1781 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 73 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.7552G>A	p.Val2518Ile	missense_variant	46/82	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.7552G>A	p.Val2518Ile	missense_variant	46/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000605912.1 linkuse as main transcript	c.112G>A	p.Val38Ile	missense_variant	1/4	3		ENSP00000476068

Frequencies

GnomAD3 genomes

AF:

0.0256

AC:

3900

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00760

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0412

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0269

AC:

6695

AN:

249220

Hom.:

122

AF XY:

0.0269

AC XY:

3641

AN XY:

135208

show subpopulations

Gnomad AFR exome

AF:

0.00588

Gnomad AMR exome

AF:

0.0166

Gnomad ASJ exome

AF:

0.0245

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00484

Gnomad FIN exome

AF:

0.0210

Gnomad NFE exome

AF:

0.0445

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.0369

AC:

53881

AN:

1461658

Hom.:

1171

Cov.:

AF XY:

0.0358

AC XY:

26055

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00544

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.0245

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00547

Gnomad4 FIN exome

AF:

0.0220

Gnomad4 NFE exome

AF:

0.0438

Gnomad4 OTH exome

AF:

0.0308

GnomAD4 genome

AF:

0.0256

AC:

3900

AN:

152268

Hom.:

Cov.:

AF XY:

0.0239

AC XY:

1781

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00758

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.0412

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.0379

Hom.:

196

Bravo

AF:

0.0256

TwinsUK

AF:

0.0426

AC:

158

ALSPAC

AF:

0.0428

AC:

165

ESP6500AA

AF:

0.00652

AC:

ESP6500EA

AF:

0.0416

AC:

344

ExAC

AF:

0.0284

AC:

3434

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0437

EpiControl

AF:

0.0429

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	Val2518Ile in exon 46 of DNAH11: This variant is not expected to have clinical s ignificance because it has been identified in 4.2% (344/8268) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs68023059). -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 08, 2020

This variant is associated with the following publications: (PMID: 24450482) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.092

.;.;T;.

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.86

D;D;D;D

MetaRNN

Benign

0.0034

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.96

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.80

.;N;.;.

REVEL

Benign

0.044

Sift

Benign

0.19

.;T;.;.

Sift4G

Benign

0.35

.;.;.;T

Vest4

0.13

ClinPred

0.0058

GERP RS

2.2

Varity_R

0.056

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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