7-21725834-C-T

Position:

• chr7-21725834-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.7290C>T​(p.Phe2430=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 1,609,990 control chromosomes in the GnomAD database, including 201,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14627 hom., cov: 32)
  • Exomes 𝑓: 0.50 (186811 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 2.22

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=-0.32).
• BP6: Variant 7-21725834-C-T is Benign according to our data. Variant chr7-21725834-C-T is described in ClinVar as [Benign]. Clinvar id is 93694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21725834-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.7290C>T	p.Phe2430=	synonymous_variant	45/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.7290C>T	p.Phe2430=	synonymous_variant	45/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64490 AN: 151802 Hom.: 14635 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.484

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.429

GnomAD3 exomes AF: 0.453 AC: 110673 AN: 244124 Hom.: 26355 AF XY: 0.464 AC XY: 61356 AN XY: 132198

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.416

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.201

Gnomad SAS exome AF: 0.524

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.510

Gnomad OTH exome AF: 0.465

GnomAD4 exome AF: 0.501 AC: 730108 AN: 1458070 Hom.: 186811 Cov.: 39 AF XY: 0.502 AC XY: 364277 AN XY: 724940

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.418

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.228

Gnomad4 SAS exome AF: 0.533

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.523

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.424 AC: 64482 AN: 151920 Hom.: 14627 Cov.: 32 AF XY: 0.424 AC XY: 31437 AN XY: 74222

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.430

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.484

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.425

Alfa AF: 0.475 Hom.: 28780

Bravo AF: 0.410

Asia WGS AF: 0.318 AC: 1103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 11, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Phe2430Phe in exon 45 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 49.2% (4012/8162) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs12536928). -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	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	-0.32
CADD	Benign	6.6
DANN	Benign	0.76

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: rs12536928; hg19: chr7-21765452; COSMIC: COSV60966351;