chr7-21703356-A-G

Variant names:

• chr7-21703356-A-G
• rs368331
• NM_001277115.2:c.6273+554A>G

Variant summary

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

The NM_001277115.2(DNAH11):​c.6273+554A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 155,720 control chromosomes in the GnomAD database, including 269 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 0.048 (260 hom., cov: 32)
  • Exomes 𝑓: 0.055 (9 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 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.6273+554A>G		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.6273+554A>G		intron	N/A	ENSP00000475939.1
	DNAH11	ENST00000465129.1	TSL:3	n.94-93A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0482 AC: 7335 AN: 152148 Hom.: 262 Cov.: 32

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0490

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0635

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0553 AC: 191 AN: 3454 Hom.: 9 AF XY: 0.0629 AC XY: 115 AN XY: 1828

African (AFR) AF: 0.00 AC: 0 AN: 26

American (AMR) AF: 0.0278 AC: 1 AN: 36

Ashkenazi Jewish (ASJ) AF: 0.0556 AC: 3 AN: 54

East Asian (EAS) AF: 0.0667 AC: 2 AN: 30

South Asian (SAS) AF: 0.0822 AC: 12 AN: 146

European-Finnish (FIN) AF: 0.0652 AC: 9 AN: 138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 22

European-Non Finnish (NFE) AF: 0.0538 AC: 150 AN: 2788

Other (OTH) AF: 0.0654 AC: 14 AN: 214

GnomAD4 genome AF: 0.0482 AC: 7333 AN: 152266 Hom.: 260 Cov.: 32 AF XY: 0.0484 AC XY: 3606 AN XY: 74466

African (AFR) AF: 0.0108 AC: 450 AN: 41552

American (AMR) AF: 0.0245 AC: 375 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0490 AC: 170 AN: 3472

East Asian (EAS) AF: 0.144 AC: 743 AN: 5174

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4826

European-Finnish (FIN) AF: 0.0603 AC: 640 AN: 10608

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0635 AC: 4320 AN: 68016

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.0584 Hom.: 1324

Bravo AF: 0.0443

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.37
DANN	Benign	0.54
PhyloP100		-0.17
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: rs368331; hg19: chr7-21742974;