chr7-21570073-C-T

Variant names:

• chr7-21570073-C-T
• rs72655982
• NM_001277115.2:c.1199C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.1199C>T​(p.Thr400Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,597,816 control chromosomes in the GnomAD database, including 1,819 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (139 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1680 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.762
• 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: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC105375183 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-21570073-C-T is Benign according to our data. Variant chr7-21570073-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 163095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0568 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.1199C>T	p.Thr400Ile	missense	Exon 7 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.1199C>T	p.Thr400Ile	missense	Exon 7 of 82	ENSP00000475939.1
	DNAH11	ENST00000496218.1	TSL:2	n.85C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6217 AN: 152120 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0201

Gnomad SAS AF: 0.0623

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.0397

GnomAD2 exomes AF: 0.0395 AC: 9028 AN: 228282 AF XY: 0.0413

Gnomad AFR exome AF: 0.0379

Gnomad AMR exome AF: 0.0130

Gnomad ASJ exome AF: 0.0468

Gnomad EAS exome AF: 0.0241

Gnomad FIN exome AF: 0.0351

Gnomad NFE exome AF: 0.0467

Gnomad OTH exome AF: 0.0362

GnomAD4 exome AF: 0.0452 AC: 65374 AN: 1445578 Hom.: 1680 Cov.: 30 AF XY: 0.0456 AC XY: 32710 AN XY: 717892

African (AFR) AF: 0.0422 AC: 1385 AN: 32852

American (AMR) AF: 0.0143 AC: 604 AN: 42152

Ashkenazi Jewish (ASJ) AF: 0.0447 AC: 1145 AN: 25638

East Asian (EAS) AF: 0.0131 AC: 515 AN: 39346

South Asian (SAS) AF: 0.0560 AC: 4656 AN: 83112

European-Finnish (FIN) AF: 0.0374 AC: 1972 AN: 52794

Middle Eastern (MID) AF: 0.0379 AC: 216 AN: 5698

European-Non Finnish (NFE) AF: 0.0474 AC: 52322 AN: 1104230

Other (OTH) AF: 0.0428 AC: 2559 AN: 59756

GnomAD4 genome AF: 0.0408 AC: 6215 AN: 152238 Hom.: 139 Cov.: 32 AF XY: 0.0403 AC XY: 3001 AN XY: 74430

African (AFR) AF: 0.0407 AC: 1693 AN: 41548

American (AMR) AF: 0.0205 AC: 313 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5174

South Asian (SAS) AF: 0.0626 AC: 302 AN: 4824

European-Finnish (FIN) AF: 0.0365 AC: 387 AN: 10604

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3152 AN: 68000

Other (OTH) AF: 0.0393 AC: 83 AN: 2114

Alfa AF: 0.0448 Hom.: 513

Bravo AF: 0.0384

TwinsUK AF: 0.0515 AC: 191

ALSPAC AF: 0.0483 AC: 186

ESP6500AA AF: 0.0407 AC: 150

ESP6500EA AF: 0.0441 AC: 360

ExAC AF: 0.0394 AC: 4748

Asia WGS AF: 0.0410 AC: 143 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 21, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Thr400Ile in exon 7 of DNAH11: This variant is not expected to have clinical sig nificance because it has been identified in 4.4% (360/8170) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs72655982).

Primary ciliary dyskinesia Benign:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Dec 31, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.33
DANN	Benign	0.30
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.020	T
MetaRNN	Benign	0.0024	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.76
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.037
Sift	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.037
ClinPred		0.00038	T
GERP RS		-5.2
Varity_R		0.047
gMVP		0.066
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.28		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.28		Position offset: -4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72655982; hg19: chr7-21609691; COSMIC: COSV99080602;