rs2285947

Variant names:

• chr7-21544470-G-A
• rs2285947
• NM_001277115.2:c.352-536G>A

Variant summary

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

The NM_001277115.2(DNAH11):​c.352-536G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,966 control chromosomes in the GnomAD database, including 15,245 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 0.44 (15245 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 34 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.352-536G>A		intron_variant	Intron 1 of 81	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.352-536G>A		intron_variant	Intron 1 of 81	5	NM_001277115.2	ENSP00000475939.1
DNAH11	ENST00000607050.1	n.342-536G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67249 AN: 151848 Hom.: 15225 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.456

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

GnomAD4 genome AF: 0.443 AC: 67307 AN: 151966 Hom.: 15245 Cov.: 32 AF XY: 0.438 AC XY: 32571 AN XY: 74284

African (AFR) AF: 0.424 AC: 17558 AN: 41438

American (AMR) AF: 0.355 AC: 5428 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1651 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1358 AN: 5170

South Asian (SAS) AF: 0.489 AC: 2357 AN: 4818

European-Finnish (FIN) AF: 0.416 AC: 4392 AN: 10548

Middle Eastern (MID) AF: 0.527 AC: 154 AN: 292

European-Non Finnish (NFE) AF: 0.488 AC: 33175 AN: 67928

Other (OTH) AF: 0.452 AC: 955 AN: 2112

Alfa AF: 0.467 Hom.: 33840

Bravo AF: 0.436

Asia WGS AF: 0.334 AC: 1160 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.42
PhyloP100		-0.12
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: rs2285947; hg19: chr7-21584088;