chr7-21570073-C-T

Position:

• chr7-21570073-C-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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]

LOC105375183 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 163095.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21570073-C-T is described in Lovd as [Benign]. Variant chr7-21570073-C-T is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.1199C>T	p.Thr400Ile	missense_variant	7/82	ENST00000409508.8	NP_001264044.1
LOC105375183	XR_007060247.1	n.282+3253G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.1199C>T	p.Thr400Ile	missense_variant	7/82	5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000496218.1	n.85C>T		non_coding_transcript_exon_variant	2/2	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

GnomAD3 exomes AF: 0.0395 AC: 9028 AN: 228282 Hom.: 215 AF XY: 0.0413 AC XY: 5102 AN XY: 123640

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 SAS exome AF: 0.0550

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

Gnomad4 AFR exome AF: 0.0422

Gnomad4 AMR exome AF: 0.0143

Gnomad4 ASJ exome AF: 0.0447

Gnomad4 EAS exome AF: 0.0131

Gnomad4 SAS exome AF: 0.0560

Gnomad4 FIN exome AF: 0.0374

Gnomad4 NFE exome AF: 0.0474

Gnomad4 OTH exome AF: 0.0428

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

Gnomad4 AFR AF: 0.0407

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0201

Gnomad4 SAS AF: 0.0626

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0464

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0450 Hom.: 244

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

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 31, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

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;T;T
MetaRNN	Benign	0.0024	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;.;N
MutationTaster	Benign	1.0	N
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

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

Publications

LitVar

Other links and lift over

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