7-21738831-C-T

Position:

• chr7-21738831-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.7776C>T​(p.His2592=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.457

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]

ACMG classification

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/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.7776C>T	p.His2592=	synonymous_variant	47/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.7776C>T	p.His2592=	synonymous_variant	47/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000605912.1	c.336C>T	p.His112=	synonymous_variant	2/4	3		ENSP00000476068

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97336 AN: 151746 Hom.: 31899 Cov.: 30

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

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.: 48 AF XY: 0.672 AC XY: 484776 AN XY: 720924

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.: 30 AF XY: 0.636 AC XY: 47210 AN XY: 74228

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

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Primary ciliary dyskinesia 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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

Other links and lift over

dbSNP: rs1109806; hg19: chr7-21778449; COSMIC: COSV60966411;