7-21821494-C-T

Variant names:

• chr7-21821494-C-T
• rs2390593
• NM_001277115.2:c.10691+3155C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277115.2(DNAH11):​c.10691+3155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,124 control chromosomes in the GnomAD database, including 60,458 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60458 hom., cov: 30)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.915 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.10691+3155C>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.10691+3155C>T		intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135357 AN: 152006 Hom.: 60437 Cov.: 30

Gnomad AFR AF: 0.833

Gnomad AMI AF: 0.923

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.914

Gnomad EAS AF: 0.893

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.899

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.890 AC: 135431 AN: 152124 Hom.: 60458 Cov.: 30 AF XY: 0.890 AC XY: 66157 AN XY: 74372

African (AFR) AF: 0.832 AC: 34514 AN: 41472

American (AMR) AF: 0.906 AC: 13852 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.914 AC: 3169 AN: 3468

East Asian (EAS) AF: 0.893 AC: 4617 AN: 5168

South Asian (SAS) AF: 0.816 AC: 3931 AN: 4818

European-Finnish (FIN) AF: 0.920 AC: 9750 AN: 10602

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62591 AN: 67992

Other (OTH) AF: 0.897 AC: 1895 AN: 2112

Alfa AF: 0.910 Hom.: 17503

Bravo AF: 0.889

Asia WGS AF: 0.848 AC: 2951 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.70
DANN	Benign	0.59
PhyloP100		-0.91
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: rs2390593; hg19: chr7-21861112;