chr7-21620027-T-C

Variant names:

• chr7-21620027-T-C
• rs56029521
• NM_001277115.2:c.4449T>C

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.4449T>C​(p.Ile1483Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,604,984 control chromosomes in the GnomAD database, including 137,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12391 hom., cov: 32)
  • Exomes 𝑓: 0.41 (125213 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.0640
• Publications: 14 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=-0.59).
• BP6: Variant 7-21620027-T-C is Benign according to our data. Variant chr7-21620027-T-C is described in ClinVar as Benign. ClinVar VariationId is 93690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.064 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 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.4449T>C	p.Ile1483Ile	synonymous	Exon 25 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.4449T>C	p.Ile1483Ile	synonymous	Exon 25 of 82	ENSP00000475939.1
	DNAH11	ENST00000465593.1	TSL:2	n.475T>C		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60279 AN: 151886 Hom.: 12397 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.385

GnomAD2 exomes AF: 0.388 AC: 94695 AN: 244116 AF XY: 0.390

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.686

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.374

GnomAD4 exome AF: 0.410 AC: 596056 AN: 1452980 Hom.: 125213 Cov.: 33 AF XY: 0.408 AC XY: 294430 AN XY: 722386

African (AFR) AF: 0.369 AC: 12236 AN: 33196

American (AMR) AF: 0.275 AC: 11979 AN: 43552

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 8612 AN: 26006

East Asian (EAS) AF: 0.670 AC: 26384 AN: 39364

South Asian (SAS) AF: 0.327 AC: 27467 AN: 83934

European-Finnish (FIN) AF: 0.388 AC: 20693 AN: 53288

Middle Eastern (MID) AF: 0.347 AC: 1993 AN: 5750

European-Non Finnish (NFE) AF: 0.417 AC: 462161 AN: 1107838

Other (OTH) AF: 0.408 AC: 24531 AN: 60052

GnomAD4 genome AF: 0.397 AC: 60294 AN: 152004 Hom.: 12391 Cov.: 32 AF XY: 0.393 AC XY: 29201 AN XY: 74310

African (AFR) AF: 0.378 AC: 15657 AN: 41448

American (AMR) AF: 0.338 AC: 5155 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3610 AN: 5172

South Asian (SAS) AF: 0.343 AC: 1652 AN: 4816

European-Finnish (FIN) AF: 0.380 AC: 4012 AN: 10562

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27818 AN: 67966

Other (OTH) AF: 0.384 AC: 812 AN: 2116

Alfa AF: 0.389 Hom.: 10055

Bravo AF: 0.397

Asia WGS AF: 0.481 AC: 1670 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	3.9
DANN	Benign	0.57
PhyloP100		-0.064
Mutation Taster		=99/1	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: rs56029521; hg19: chr7-21659645; COSMIC: COSV60946229;