NM_001277115.2:c.10691+2164G>C

Variant names:

• chr7-21820503-G-C
• rs6969326
• NM_001277115.2:c.10691+2164G>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.10691+2164G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 152,000 control chromosomes in the GnomAD database, including 18,786 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 0.48 (18786 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 0 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 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+2164G>C		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+2164G>C		intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73169 AN: 151882 Hom.: 18783 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.482 AC: 73201 AN: 152000 Hom.: 18786 Cov.: 32 AF XY: 0.474 AC XY: 35199 AN XY: 74278

African (AFR) AF: 0.372 AC: 15416 AN: 41438

American (AMR) AF: 0.413 AC: 6303 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2245 AN: 3470

East Asian (EAS) AF: 0.0795 AC: 411 AN: 5170

South Asian (SAS) AF: 0.382 AC: 1843 AN: 4822

European-Finnish (FIN) AF: 0.557 AC: 5885 AN: 10558

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39354 AN: 67972

Other (OTH) AF: 0.491 AC: 1037 AN: 2110

Alfa AF: 0.404 Hom.: 1194

Bravo AF: 0.467

Asia WGS AF: 0.271 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.69
PhyloP100		0.023
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: rs6969326; hg19: chr7-21860121;