rs17144835

Variant names:

• chr7-21639025-A-G
• rs17144835
• NM_001277115.2:c.4904A>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.4904A>G​(p.Asp1635Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0471 in 1,613,206 control chromosomes in the GnomAD database, including 2,010 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.052 (240 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1770 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 7.14
• Publications: 16 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004967749).
• BP6: Variant 7-21639025-A-G is Benign according to our data. Variant chr7-21639025-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0686 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.4904A>G	p.Asp1635Gly	missense	Exon 28 of 82	NP_001264044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.4904A>G	p.Asp1635Gly	missense	Exon 28 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7933 AN: 152098 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.0710

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.0342

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0364

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0478

Gnomad OTH AF: 0.0547

GnomAD2 exomes AF: 0.0443 AC: 10999 AN: 248486 AF XY: 0.0446

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.0229

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.00323

Gnomad FIN exome AF: 0.0351

Gnomad NFE exome AF: 0.0495

Gnomad OTH exome AF: 0.0500

GnomAD4 exome AF: 0.0465 AC: 67984 AN: 1460990 Hom.: 1770 Cov.: 30 AF XY: 0.0466 AC XY: 33854 AN XY: 726750

African (AFR) AF: 0.0701 AC: 2347 AN: 33458

American (AMR) AF: 0.0246 AC: 1099 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2832 AN: 26096

East Asian (EAS) AF: 0.00118 AC: 47 AN: 39680

South Asian (SAS) AF: 0.0432 AC: 3722 AN: 86102

European-Finnish (FIN) AF: 0.0373 AC: 1989 AN: 53382

Middle Eastern (MID) AF: 0.0694 AC: 400 AN: 5764

European-Non Finnish (NFE) AF: 0.0471 AC: 52366 AN: 1111498

Other (OTH) AF: 0.0527 AC: 3182 AN: 60352

GnomAD4 genome AF: 0.0521 AC: 7929 AN: 152216 Hom.: 240 Cov.: 32 AF XY: 0.0505 AC XY: 3761 AN XY: 74418

African (AFR) AF: 0.0707 AC: 2937 AN: 41524

American (AMR) AF: 0.0341 AC: 522 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5176

South Asian (SAS) AF: 0.0464 AC: 224 AN: 4826

European-Finnish (FIN) AF: 0.0364 AC: 386 AN: 10604

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

European-Non Finnish (NFE) AF: 0.0478 AC: 3251 AN: 68010

Other (OTH) AF: 0.0541 AC: 114 AN: 2106

Alfa AF: 0.0497 Hom.: 776

Bravo AF: 0.0520

TwinsUK AF: 0.0469 AC: 174

ALSPAC AF: 0.0516 AC: 199

ESP6500AA AF: 0.0687 AC: 258

ESP6500EA AF: 0.0461 AC: 378

ExAC AF: 0.0452 AC: 5458

Asia WGS AF: 0.0340 AC: 120 AN: 3478

EpiCase AF: 0.0474

EpiControl AF: 0.0445

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-0.89	T
PhyloP100		7.1
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0020	D
Vest4		0.29
ClinPred		0.10	T
GERP RS		5.8
Varity_R		0.82
gMVP		0.65
Mutation Taster		=43/57	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: rs17144835; hg19: chr7-21678643; COSMIC: COSV99080605; COSMIC: COSV99080605;