rs10248618

Variant names:

• chr7-21788462-C-T
• rs10248618
• NM_001277115.2:c.9925-779C>T

Variant summary

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

The NM_001277115.2(DNAH11):​c.9925-779C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 151,682 control chromosomes in the GnomAD database, including 1,551 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 0.13 (1551 hom., cov: 32)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 5 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), Laboratory for Molecular Medicine, 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 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.9925-779C>T		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.9925-779C>T		intron	N/A	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18951 AN: 151562 Hom.: 1548 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.0863

Gnomad ASJ AF: 0.0708

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.0643

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.157

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.125 AC: 18967 AN: 151682 Hom.: 1551 Cov.: 32 AF XY: 0.126 AC XY: 9345 AN XY: 74104

African (AFR) AF: 0.220 AC: 9071 AN: 41304

American (AMR) AF: 0.0859 AC: 1311 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0708 AC: 245 AN: 3462

East Asian (EAS) AF: 0.274 AC: 1394 AN: 5092

South Asian (SAS) AF: 0.0635 AC: 305 AN: 4802

European-Finnish (FIN) AF: 0.114 AC: 1202 AN: 10498

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.0748 AC: 5082 AN: 67964

Other (OTH) AF: 0.126 AC: 265 AN: 2102

Alfa AF: 0.0887 Hom.: 1257

Bravo AF: 0.131

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.62
PhyloP100		-1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10248618;

hg19: chr7-21828080;