7-21559615-C-T

Position:

• chr7-21559615-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.705C>T​(p.Asn235Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,593,732 control chromosomes in the GnomAD database, including 158,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16846 hom., cov: 32)
  • Exomes 𝑓: 0.44 (141880 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.401

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 7-21559615-C-T is Benign according to our data. Variant chr7-21559615-C-T is described in ClinVar as [Benign]. Clinvar id is 93693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21559615-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.401 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.705C>T	p.Asn235Asn	synonymous_variant	4/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.705C>T	p.Asn235Asn	synonymous_variant	4/82	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70261 AN: 151730 Hom.: 16817 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.456

GnomAD3 exomes AF: 0.447 AC: 105203 AN: 235568 Hom.: 24791 AF XY: 0.450 AC XY: 57482 AN XY: 127642

Gnomad AFR exome AF: 0.533

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.746

Gnomad SAS exome AF: 0.524

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.438 AC: 631657 AN: 1441884 Hom.: 141880 Cov.: 32 AF XY: 0.440 AC XY: 314957 AN XY: 716552

Gnomad4 AFR exome AF: 0.537

Gnomad4 AMR exome AF: 0.335

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.699

Gnomad4 SAS exome AF: 0.530

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.454

GnomAD4 genome AF: 0.463 AC: 70339 AN: 151848 Hom.: 16846 Cov.: 32 AF XY: 0.464 AC XY: 34432 AN XY: 74204

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.749

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.457

Alfa AF: 0.423 Hom.: 22341

Bravo AF: 0.463

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Asn235Asn in exon 4 of DNAH11: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 47.0% (1718/3656) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs10950854). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Primary ciliary dyskinesia Benign:2

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

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	-0.38
CADD	Benign	3.8
DANN	Benign	0.65

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

Other links and lift over

dbSNP: rs10950854; hg19: chr7-21599233; COSMIC: COSV60940505; COSMIC: COSV60940505;