rs55666134

Variant names:

• chr7-21683813-G-A
• rs55666134
• NM_001277115.2:c.5490G>A

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.5490G>A​(p.Leu1830Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,610,424 control chromosomes in the GnomAD database, including 17,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1229 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16065 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.377
• Publications: 15 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), ClinGen, Laboratory for Molecular Medicine
• 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=-0.56).
• BP6: Variant 7-21683813-G-A is Benign according to our data. Variant chr7-21683813-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.154 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.5490G>A	p.Leu1830Leu	synonymous	Exon 32 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.5490G>A	p.Leu1830Leu	synonymous	Exon 32 of 82	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17819 AN: 152060 Hom.: 1230 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.119

GnomAD2 exomes AF: 0.129 AC: 31967 AN: 247102 AF XY: 0.132

Gnomad AFR exome AF: 0.0372

Gnomad AMR exome AF: 0.0725

Gnomad ASJ exome AF: 0.153

Gnomad EAS exome AF: 0.141

Gnomad FIN exome AF: 0.157

Gnomad NFE exome AF: 0.156

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.145 AC: 211014 AN: 1458246 Hom.: 16065 Cov.: 31 AF XY: 0.144 AC XY: 104462 AN XY: 725222

African (AFR) AF: 0.0350 AC: 1170 AN: 33418

American (AMR) AF: 0.0764 AC: 3396 AN: 44464

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4075 AN: 25968

East Asian (EAS) AF: 0.140 AC: 5549 AN: 39646

South Asian (SAS) AF: 0.109 AC: 9349 AN: 85498

European-Finnish (FIN) AF: 0.157 AC: 8344 AN: 53246

Middle Eastern (MID) AF: 0.115 AC: 662 AN: 5748

European-Non Finnish (NFE) AF: 0.153 AC: 170290 AN: 1110014

Other (OTH) AF: 0.136 AC: 8179 AN: 60244

GnomAD4 genome AF: 0.117 AC: 17820 AN: 152178 Hom.: 1229 Cov.: 32 AF XY: 0.117 AC XY: 8688 AN XY: 74388

African (AFR) AF: 0.0420 AC: 1747 AN: 41552

American (AMR) AF: 0.101 AC: 1539 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 553 AN: 3468

East Asian (EAS) AF: 0.141 AC: 732 AN: 5182

South Asian (SAS) AF: 0.111 AC: 535 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1642 AN: 10568

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10662 AN: 67978

Other (OTH) AF: 0.118 AC: 250 AN: 2114

Alfa AF: 0.142 Hom.: 5828

Bravo AF: 0.109

Asia WGS AF: 0.123 AC: 427 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)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs55666134; hg19: chr7-21723431; COSMIC: COSV60957464;