rs17745898

Variant names:

• chr7-21601000-C-G
• rs17745898
• NM_001277115.2:c.3256-10C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.3256-10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 1,610,006 control chromosomes in the GnomAD database, including 17,377 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1127 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16250 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Scores: Splicing: ADA: 0.0001173
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.160
• Publications: 12 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), ClinGen, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-21601000-C-G is Benign according to our data. Variant chr7-21601000-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 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.3256-10C>G		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.3256-10C>G		intron	N/A	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16121 AN: 152064 Hom.: 1127 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0853

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.131

GnomAD2 exomes AF: 0.116 AC: 28516 AN: 244890 AF XY: 0.122

Gnomad AFR exome AF: 0.0234

Gnomad AMR exome AF: 0.0737

Gnomad ASJ exome AF: 0.155

Gnomad EAS exome AF: 0.0324

Gnomad FIN exome AF: 0.0832

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.144 AC: 210202 AN: 1457822 Hom.: 16250 Cov.: 37 AF XY: 0.144 AC XY: 104662 AN XY: 725008

African (AFR) AF: 0.0224 AC: 740 AN: 33096

American (AMR) AF: 0.0790 AC: 3449 AN: 43648

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 4106 AN: 26064

East Asian (EAS) AF: 0.0257 AC: 1019 AN: 39676

South Asian (SAS) AF: 0.125 AC: 10641 AN: 85008

European-Finnish (FIN) AF: 0.0874 AC: 4662 AN: 53362

Middle Eastern (MID) AF: 0.167 AC: 957 AN: 5746

European-Non Finnish (NFE) AF: 0.159 AC: 176387 AN: 1110994

Other (OTH) AF: 0.137 AC: 8241 AN: 60228

GnomAD4 genome AF: 0.106 AC: 16122 AN: 152184 Hom.: 1127 Cov.: 32 AF XY: 0.103 AC XY: 7656 AN XY: 74410

African (AFR) AF: 0.0275 AC: 1141 AN: 41514

American (AMR) AF: 0.112 AC: 1710 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.165 AC: 574 AN: 3470

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5186

South Asian (SAS) AF: 0.118 AC: 569 AN: 4820

European-Finnish (FIN) AF: 0.0853 AC: 904 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10690 AN: 67996

Other (OTH) AF: 0.129 AC: 272 AN: 2114

Alfa AF: 0.129 Hom.: 277

Bravo AF: 0.105

Asia WGS AF: 0.0550 AC: 195 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	2	Primary ciliary dyskinesia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.6
DANN	Benign	0.33
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00012
dbscSNV1_RF	Benign	0.042
SpliceAI score (max)		0.080		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: rs17745898; hg19: chr7-21640618; COSMIC: COSV60953433;