rs729657

Variant names:

• chr7-21744419-C-T
• rs729657
• NM_001277115.2:c.8155-19C>T

Variant summary

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

The ENST00000409508.8(DNAH11):​c.8155-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,609,344 control chromosomes in the GnomAD database, including 6,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (338 hom., cov: 33)
  • Exomes 𝑓: 0.084 (5674 hom.)
• Consequence: DNAH11 ENST00000409508.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.211
• Publications: 7 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: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• 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=-0.75).
• BP6: Variant 7-21744419-C-T is Benign according to our data. Variant chr7-21744419-C-T is described in ClinVar as Benign. ClinVar VariationId is 257934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409508.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.8155-19C>T		intron	N/A	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.8155-19C>T		intron	N/A	ENSP00000475939.1
	DNAH11	ENST00000605912.1	TSL:3	c.475-451C>T		intron	N/A	ENSP00000476068.1

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8567 AN: 152068 Hom.: 336 Cov.: 33

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0527

GnomAD2 exomes AF: 0.0652 AC: 16015 AN: 245636 AF XY: 0.0675

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0478

Gnomad ASJ exome AF: 0.0431

Gnomad EAS exome AF: 0.00174

Gnomad FIN exome AF: 0.0656

Gnomad NFE exome AF: 0.0863

Gnomad OTH exome AF: 0.0681

GnomAD4 exome AF: 0.0841 AC: 122612 AN: 1457156 Hom.: 5674 Cov.: 31 AF XY: 0.0838 AC XY: 60693 AN XY: 724598

African (AFR) AF: 0.0141 AC: 467 AN: 33206

American (AMR) AF: 0.0481 AC: 2109 AN: 43820

Ashkenazi Jewish (ASJ) AF: 0.0460 AC: 1198 AN: 26054

East Asian (EAS) AF: 0.000933 AC: 37 AN: 39646

South Asian (SAS) AF: 0.0781 AC: 6625 AN: 84864

European-Finnish (FIN) AF: 0.0663 AC: 3539 AN: 53354

Middle Eastern (MID) AF: 0.0620 AC: 357 AN: 5756

European-Non Finnish (NFE) AF: 0.0934 AC: 103677 AN: 1110234

Other (OTH) AF: 0.0764 AC: 4603 AN: 60222

GnomAD4 genome AF: 0.0563 AC: 8569 AN: 152188 Hom.: 338 Cov.: 33 AF XY: 0.0550 AC XY: 4093 AN XY: 74404

African (AFR) AF: 0.0158 AC: 658 AN: 41528

American (AMR) AF: 0.0434 AC: 663 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5182

South Asian (SAS) AF: 0.0682 AC: 329 AN: 4822

European-Finnish (FIN) AF: 0.0644 AC: 682 AN: 10582

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0870 AC: 5918 AN: 67998

Other (OTH) AF: 0.0522 AC: 110 AN: 2108

Alfa AF: 0.0795 Hom.: 317

Bravo AF: 0.0524

Asia WGS AF: 0.0280 AC: 96 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.1
DANN	Benign	0.62
PhyloP100		0.21
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: rs729657; hg19: chr7-21784037;