Genetic Variant NM_001277115.2:c.7776C>T (chr7-21738831-C-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_001277115.2(DNAH11):c.7776C>T(p.His2592His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 1,603,266 control chromosomes in the GnomAD database, including 366,485 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31924 hom., cov: 30)

Exomes 𝑓: 0.67 ( 334561 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.457

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 7-21738831-C-T is Benign according to our data. Variant chr7-21738831-C-T is described in ClinVar as [Benign]. Clinvar id is 163112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21738831-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2 link	c.7776C>T	p.His2592His	synonymous_variant	Exon 47 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.7776C>T	p.His2592His	synonymous_variant	Exon 47 of 82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5
DNAH11	ENST00000605912.1 link	c.336C>T	p.His112His	synonymous_variant	Exon 2 of 4	3		ENSP00000476068.1		U3KQN2

Frequencies

GnomAD3 genomes

AF:

0.641

AC:

97336

AN:

151746

Hom.:

31899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.607

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.622

Gnomad EAS

AF:

0.237

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.640

GnomAD3 exomes

AF:

0.612

AC:

144780

AN:

236554

Hom.:

46366

AF XY:

0.621

AC XY:

79336

AN XY:

127698

show subpopulations

Gnomad AFR exome

AF:

0.599

Gnomad AMR exome

AF:

0.511

Gnomad ASJ exome

AF:

0.611

Gnomad EAS exome

AF:

0.222

Gnomad SAS exome

AF:

0.616

Gnomad FIN exome

AF:

0.676

Gnomad NFE exome

AF:

0.694

Gnomad OTH exome

AF:

0.643

GnomAD4 exome

AF:

0.673

AC:

976458

AN:

1451402

Hom.:

334561

Cov.:

AF XY:

0.672

AC XY:

484776

AN XY:

720924

show subpopulations

Gnomad4 AFR exome

AF:

0.617

Gnomad4 AMR exome

AF:

0.521

Gnomad4 ASJ exome

AF:

0.610

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.623

Gnomad4 FIN exome

AF:

0.676

Gnomad4 NFE exome

AF:

0.703

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.641

AC:

97398

AN:

151864

Hom.:

31924

Cov.:

AF XY:

0.636

AC XY:

47210

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.608

Gnomad4 AMR

AF:

0.599

Gnomad4 ASJ

AF:

0.622

Gnomad4 EAS

AF:

0.236

Gnomad4 SAS

AF:

0.595

Gnomad4 FIN

AF:

0.686

Gnomad4 NFE

AF:

0.698

Gnomad4 OTH

AF:

0.641

Alfa

AF:

0.673

Hom.:

67214

Bravo

AF:

0.628

Asia WGS

AF:

0.453

AC:

1576

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

His2592His in exon 47 of DNAH11: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 38.9% (1692/4352) of African American chromosomes from a broad population by the NHLBI Exome Sequ encing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1109806). -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Primary ciliary dyskinesia

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 7

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.3

DANN

Benign

0.32

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