rs6461593

Variant names:

• chr7-21664387-T-C
• rs6461593
• NM_001277115.2:c.5328+5356T>C

Variant summary

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

The NM_001277115.2(DNAH11):​c.5328+5356T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 151,748 control chromosomes in the GnomAD database, including 4,654 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 0.22 (4654 hom., cov: 30)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.5328+5356T>C		intron_variant	Intron 30 of 81	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.5328+5356T>C		intron_variant	Intron 30 of 81	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33588 AN: 151630 Hom.: 4644 Cov.: 30

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.222 AC: 33613 AN: 151748 Hom.: 4654 Cov.: 30 AF XY: 0.216 AC XY: 16045 AN XY: 74180

African (AFR) AF: 0.392 AC: 16168 AN: 41270

American (AMR) AF: 0.136 AC: 2071 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3468

East Asian (EAS) AF: 0.00329 AC: 17 AN: 5172

South Asian (SAS) AF: 0.177 AC: 852 AN: 4814

European-Finnish (FIN) AF: 0.126 AC: 1336 AN: 10564

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11579 AN: 67920

Other (OTH) AF: 0.198 AC: 417 AN: 2104

Alfa AF: 0.183 Hom.: 4247

Bravo AF: 0.229

Asia WGS AF: 0.0960 AC: 336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.89
DANN	Benign	0.34
PhyloP100		-0.72
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: rs6461593; hg19: chr7-21704005;