rs2285942

Variant names:

• chr7-21543299-C-T
• rs2285942
• NM_001277115.2:c.54C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.54C>T​(p.Thr18Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,548,618 control chromosomes in the GnomAD database, including 14,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (932 hom., cov: 33)
  • Exomes 𝑓: 0.14 (13870 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.521

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 7-21543299-C-T is Benign according to our data. Variant chr7-21543299-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 178721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21543299-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.521 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.54C>T	p.Thr18Thr	synonymous_variant	Exon 1 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.54C>T	p.Thr18Thr	synonymous_variant	Exon 1 of 82	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000607050.1	n.-147C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14999 AN: 152088 Hom.: 932 Cov.: 33

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0846

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.0589

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.0984

GnomAD3 exomes AF: 0.100 AC: 15074 AN: 150352 Hom.: 933 AF XY: 0.101 AC XY: 8133 AN XY: 80262

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.0596

Gnomad ASJ exome AF: 0.0843

Gnomad EAS exome AF: 0.0439

Gnomad SAS exome AF: 0.0615

Gnomad FIN exome AF: 0.144

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.0996

GnomAD4 exome AF: 0.136 AC: 189940 AN: 1396412 Hom.: 13870 Cov.: 32 AF XY: 0.134 AC XY: 92020 AN XY: 688484

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.0664

Gnomad4 ASJ exome AF: 0.0873

Gnomad4 EAS exome AF: 0.0779

Gnomad4 SAS exome AF: 0.0650

Gnomad4 FIN exome AF: 0.146

Gnomad4 NFE exome AF: 0.151

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.0985 AC: 14998 AN: 152206 Hom.: 932 Cov.: 33 AF XY: 0.0955 AC XY: 7108 AN XY: 74418

Gnomad4 AFR AF: 0.0326

Gnomad4 AMR AF: 0.0844

Gnomad4 ASJ AF: 0.0766

Gnomad4 EAS AF: 0.0564

Gnomad4 SAS AF: 0.0585

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.144

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.134 Hom.: 2514

Bravo AF: 0.0917

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

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

Thr18Thr in exon 1 of DNAH11: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 10.9% (715/6530) of European American chromosomes from a broad population by the NHLBI Exome Sequenc ing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2285942). -

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: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 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	-0.64
CADD	Benign	3.7
DANN	Benign	0.92

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: rs2285942; hg19: chr7-21582917;