rs1023542

Variant names:

• chr7-21705443-A-G
• rs1023542
• NM_001277115.2:c.6469-17A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-21705443-A-G
• chr7-21705443-A-C
• chr7-21705443-A-T

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.6469-17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,612,334 control chromosomes in the GnomAD database, including 86,466 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (19566 hom., cov: 33)
  • Exomes 𝑓: 0.26 (66900 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.349
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-21705443-A-G is Benign according to our data. Variant chr7-21705443-A-G is described in ClinVar as Benign. ClinVar VariationId is 257920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 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.6469-17A>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.6469-17A>G		intron	N/A	ENSP00000475939.1	Q96DT5

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65257 AN: 152010 Hom.: 19511 Cov.: 33

Gnomad AFR AF: 0.814

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.366 AC: 90798 AN: 247876 AF XY: 0.350

Gnomad AFR exome AF: 0.832

Gnomad AMR exome AF: 0.536

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.744

Gnomad FIN exome AF: 0.297

Gnomad NFE exome AF: 0.204

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.262 AC: 382811 AN: 1460206 Hom.: 66900 Cov.: 32 AF XY: 0.264 AC XY: 191512 AN XY: 726344

African (AFR) AF: 0.841 AC: 28100 AN: 33422

American (AMR) AF: 0.524 AC: 23307 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 5117 AN: 26084

East Asian (EAS) AF: 0.767 AC: 30396 AN: 39652

South Asian (SAS) AF: 0.431 AC: 37113 AN: 86066

European-Finnish (FIN) AF: 0.290 AC: 15449 AN: 53334

Middle Eastern (MID) AF: 0.311 AC: 1790 AN: 5756

European-Non Finnish (NFE) AF: 0.201 AC: 223205 AN: 1111080

Other (OTH) AF: 0.304 AC: 18334 AN: 60300

GnomAD4 genome AF: 0.430 AC: 65382 AN: 152128 Hom.: 19566 Cov.: 33 AF XY: 0.437 AC XY: 32487 AN XY: 74358

African (AFR) AF: 0.814 AC: 33807 AN: 41512

American (AMR) AF: 0.443 AC: 6773 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3470

East Asian (EAS) AF: 0.742 AC: 3839 AN: 5176

South Asian (SAS) AF: 0.456 AC: 2198 AN: 4816

European-Finnish (FIN) AF: 0.295 AC: 3114 AN: 10550

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.205 AC: 13949 AN: 68002

Other (OTH) AF: 0.368 AC: 779 AN: 2114

Alfa AF: 0.286 Hom.: 11895

Bravo AF: 0.456

Asia WGS AF: 0.609 AC: 2115 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.47
DANN	Benign	0.27
PhyloP100		-0.35
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: rs1023542;

hg19: chr7-21745061;

COSMIC: COSV60957197;

COSMIC: COSV60957197;