rs17144747

Variant names:

• chr7-21599954-A-G
• rs17144747
• NM_001277115.2:c.2835A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.2835A>G​(p.Gln945Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,613,536 control chromosomes in the GnomAD database, including 2,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (516 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1955 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.12
• 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: 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-21599954-A-G is Benign according to our data. Variant chr7-21599954-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 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.2835A>G	p.Gln945Gln	synonymous	Exon 15 of 82	NP_001264044.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.2835A>G	p.Gln945Gln	synonymous	Exon 15 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10500 AN: 152072 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0593

GnomAD2 exomes AF: 0.0469 AC: 11660 AN: 248418 AF XY: 0.0467

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0485

Gnomad EAS exome AF: 0.0267

Gnomad FIN exome AF: 0.0345

Gnomad NFE exome AF: 0.0460

Gnomad OTH exome AF: 0.0413

GnomAD4 exome AF: 0.0467 AC: 68309 AN: 1461346 Hom.: 1955 Cov.: 32 AF XY: 0.0467 AC XY: 33936 AN XY: 726936

African (AFR) AF: 0.146 AC: 4886 AN: 33466

American (AMR) AF: 0.0216 AC: 964 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 1204 AN: 26130

East Asian (EAS) AF: 0.0154 AC: 610 AN: 39684

South Asian (SAS) AF: 0.0564 AC: 4859 AN: 86216

European-Finnish (FIN) AF: 0.0365 AC: 1948 AN: 53378

Middle Eastern (MID) AF: 0.0480 AC: 277 AN: 5768

European-Non Finnish (NFE) AF: 0.0454 AC: 50438 AN: 1111690

Other (OTH) AF: 0.0517 AC: 3123 AN: 60354

GnomAD4 genome AF: 0.0692 AC: 10527 AN: 152190 Hom.: 516 Cov.: 32 AF XY: 0.0673 AC XY: 5009 AN XY: 74430

African (AFR) AF: 0.140 AC: 5795 AN: 41494

American (AMR) AF: 0.0358 AC: 548 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3472

East Asian (EAS) AF: 0.0199 AC: 103 AN: 5182

South Asian (SAS) AF: 0.0622 AC: 300 AN: 4822

European-Finnish (FIN) AF: 0.0349 AC: 370 AN: 10602

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0453 AC: 3080 AN: 68010

Other (OTH) AF: 0.0587 AC: 124 AN: 2114

Alfa AF: 0.0538 Hom.: 459

Bravo AF: 0.0722

Asia WGS AF: 0.0480 AC: 168 AN: 3478

EpiCase AF: 0.0417

EpiControl AF: 0.0419

ClinVar

ClinVar submissions as Germline

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	-0.52
CADD	Benign	12
DANN	Benign	0.53
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs17144747; hg19: chr7-21639572; COSMIC: COSV60985255;