rs59447021

Variant names:

• chr7-21683955-A-T
• rs59447021
• NM_001277115.2:c.5621+11A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.5621+11A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,611,360 control chromosomes in the GnomAD database, including 34,984 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4173 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30811 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.28
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-21683955-A-T is Benign according to our data. Variant chr7-21683955-A-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93692.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 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.5621+11A>T		intron	N/A	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.5621+11A>T		intron	N/A	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35108 AN: 151968 Hom.: 4160 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.232

GnomAD2 exomes AF: 0.209 AC: 51733 AN: 247472 AF XY: 0.211

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.270

Gnomad EAS exome AF: 0.213

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.203 AC: 296909 AN: 1459274 Hom.: 30811 Cov.: 33 AF XY: 0.204 AC XY: 148402 AN XY: 725846

African (AFR) AF: 0.305 AC: 10184 AN: 33420

American (AMR) AF: 0.147 AC: 6533 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 6999 AN: 26040

East Asian (EAS) AF: 0.201 AC: 7950 AN: 39632

South Asian (SAS) AF: 0.211 AC: 18109 AN: 85724

European-Finnish (FIN) AF: 0.227 AC: 12100 AN: 53302

Middle Eastern (MID) AF: 0.231 AC: 1329 AN: 5752

European-Non Finnish (NFE) AF: 0.199 AC: 220952 AN: 1110614

Other (OTH) AF: 0.212 AC: 12753 AN: 60272

GnomAD4 genome AF: 0.231 AC: 35155 AN: 152086 Hom.: 4173 Cov.: 32 AF XY: 0.232 AC XY: 17258 AN XY: 74344

African (AFR) AF: 0.291 AC: 12070 AN: 41454

American (AMR) AF: 0.190 AC: 2906 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 994 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1068 AN: 5176

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4818

European-Finnish (FIN) AF: 0.235 AC: 2484 AN: 10590

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13742 AN: 67986

Other (OTH) AF: 0.235 AC: 494 AN: 2102

Alfa AF: 0.224 Hom.: 737

Bravo AF: 0.228

Asia WGS AF: 0.237 AC: 823 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	-0.93
CADD	Benign	0.016
DANN	Benign	0.53
PhyloP100		-1.3
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

Other links and lift over

dbSNP: rs59447021; hg19: chr7-21723573; COSMIC: COSV60946253;