rs2285942

Variant names:

• chr7-21543299-C-T
• rs2285942
• NM_001277115.2:c.54C>T
• DNAH11 p.Thr18Thr

Variant summary

Our verdict is Benign. The variant received -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:7
• Conservation: PhyloP100: -0.521
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 178721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.54C>T	p.Thr18Thr	synonymous	Exon 1 of 82	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.54C>T	p.Thr18Thr	synonymous	Exon 1 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000607050.1	TSL:3	n.-147C>T		upstream_gene	N/A

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

GnomAD2 exomes AF: 0.100 AC: 15074 AN: 150352 AF XY: 0.101

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 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

African (AFR) AF: 0.0268 AC: 845 AN: 31532

American (AMR) AF: 0.0664 AC: 2367 AN: 35654

Ashkenazi Jewish (ASJ) AF: 0.0873 AC: 2195 AN: 25142

East Asian (EAS) AF: 0.0779 AC: 2781 AN: 35702

South Asian (SAS) AF: 0.0650 AC: 5147 AN: 79140

European-Finnish (FIN) AF: 0.146 AC: 7064 AN: 48444

Middle Eastern (MID) AF: 0.0638 AC: 316 AN: 4952

European-Non Finnish (NFE) AF: 0.151 AC: 162273 AN: 1077982

Other (OTH) AF: 0.120 AC: 6952 AN: 57864

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

African (AFR) AF: 0.0326 AC: 1357 AN: 41564

American (AMR) AF: 0.0844 AC: 1291 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.0564 AC: 290 AN: 5142

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4820

European-Finnish (FIN) AF: 0.135 AC: 1428 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9786 AN: 67970

Other (OTH) AF: 0.0974 AC: 206 AN: 2116

Alfa AF: 0.130 Hom.: 3365

Bravo AF: 0.0917

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	3.7
DANN	Benign	0.92
PhyloP100		-0.52
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2285942;

hg19: chr7-21582917;

COSMIC: COSV108124250;

COSMIC: COSV108124250;