rs4722063

Variant names:

• chr7-21853886-T-C
• rs4722063
• NM_001277115.2:c.11062-429T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001277115.2(DNAH11):​c.11062-429T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 152,056 control chromosomes in the GnomAD database, including 21,305 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 0.50 (21305 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.48
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.642 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.11062-429T>C		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.11062-429T>C		intron	N/A	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000421290.1	TSL:4	n.245-429T>C		intron	N/A
	DNAH11	ENST00000607413.5	TSL:4	n.325-429T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75678 AN: 151938 Hom.: 21317 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.498 AC: 75671 AN: 152056 Hom.: 21305 Cov.: 32 AF XY: 0.488 AC XY: 36249 AN XY: 74338

African (AFR) AF: 0.263 AC: 10921 AN: 41490

American (AMR) AF: 0.457 AC: 6986 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2148 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1229 AN: 5174

South Asian (SAS) AF: 0.398 AC: 1920 AN: 4824

European-Finnish (FIN) AF: 0.624 AC: 6594 AN: 10566

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 43994 AN: 67944

Other (OTH) AF: 0.538 AC: 1133 AN: 2106

Alfa AF: 0.536 Hom.: 4101

Bravo AF: 0.477

Asia WGS AF: 0.294 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		1.5
Mutation Taster		=99/1	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: rs4722063; hg19: chr7-21893504;