rs72657342

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001277115.2(DNAH11):c.6352G>A(p.Gly2118Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000891 in 1,613,768 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00093 ( 1 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: -0.337

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.032141715).

BP6

Variant 7-21704512-G-A is Benign according to our data. Variant chr7-21704512-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 410849.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=3}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.6352G>A	p.Gly2118Ser	missense_variant	Exon 38 of 82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 link	c.6352G>A	p.Gly2118Ser	missense_variant	Exon 38 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.000487

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000486

AC:

121

AN:

248798

Hom.:

AF XY:

0.000489

AC XY:

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.000259

Gnomad AMR exome

AF:

0.0000872

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000940

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000933

AC:

1364

AN:

1461548

Hom.:

Cov.:

AF XY:

0.000883

AC XY:

642

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.000696

GnomAD4 genome

AF:

0.000486

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000881

Hom.:

Bravo

AF:

0.000412

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000253

AC:

ESP6500EA

AF:

0.00108

AC:

ExAC

AF:

0.000521

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000652

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia 7

Uncertain:2

Feb 17, 2022

Revvity Omics, Revvity

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 25, 2022

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The DNAH11 c.6352G>A; p.Gly2118Ser variant (rs72657342), to our knowledge, is not reported in the medical literature; but is reported in ClinVar (Variation ID: 410849). This variant is found in the general population with an overall allele frequency of 0.05% (132/280170 alleles) in the Genome Aggregation Database. The glycine at codon 2118 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.082). Due to limited information, the clinical significance of the this variant is uncertain at this time. -

not provided

Uncertain:1Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH11: BP4 -

Feb 13, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Primary ciliary dyskinesia

Benign:1

Nov 30, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.38

DANN

Benign

0.92

DEOGEN2

Benign

0.32

.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.82

T;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.032

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.9

.;D;.

REVEL

Benign

0.082

Sift

Benign

0.17

.;T;.

Vest4

0.21

MVP

0.048

ClinPred

0.022

GERP RS

-4.3

Varity_R

0.036

gMVP

0.33

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