rs73279826

chr7-21854462-C-Achr7-21854462-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):c.11202+7C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0248 in 1,611,074 control chromosomes in the GnomAD database, including 4,470 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (1893 hom., cov: 32)
  • Exomes 𝑓: 0.018 (2577 hom.)
• Consequence: DNAH11 NM_001277115.2 splice_region, intron
• Scores: Splicing: ADA: 0.00009980
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.127

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 7-21854462-C-A is Benign according to our data. Variant chr7-21854462-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 163123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21854462-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.11202+7C>A		splice_region_variant, intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.11202+7C>A		splice_region_variant, intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000421290.1	n.385+7C>A		splice_region_variant, intron_variant, non_coding_transcript_variant		4
DNAH11	ENST00000607413.5	n.465+7C>A		splice_region_variant, intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0934 AC: 14182 AN: 151912 Hom.: 1894 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.00691

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0510

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.0702

GnomAD3 exomes AF: 0.0427 AC: 10571 AN: 247478 Hom.: 1099 AF XY: 0.0359 AC XY: 4812 AN XY: 134162

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.0238

Gnomad ASJ exome AF: 0.00847

Gnomad EAS exome AF: 0.221

Gnomad SAS exome AF: 0.00529

Gnomad FIN exome AF: 0.0303

Gnomad NFE exome AF: 0.00253

Gnomad OTH exome AF: 0.0246

GnomAD4 exome AF: 0.0177 AC: 25775 AN: 1459044 Hom.: 2577 Cov.: 34 AF XY: 0.0162 AC XY: 11742 AN XY: 725618

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.0247

Gnomad4 ASJ exome AF: 0.00824

Gnomad4 EAS exome AF: 0.218

Gnomad4 SAS exome AF: 0.00567

Gnomad4 FIN exome AF: 0.0279

Gnomad4 NFE exome AF: 0.00161

Gnomad4 OTH exome AF: 0.0374

GnomAD4 genome AF: 0.0933 AC: 14183 AN: 152030 Hom.: 1893 Cov.: 32 AF XY: 0.0933 AC XY: 6939 AN XY: 74334

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.00691

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.00254

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0314 Hom.: 261

Bravo AF: 0.105

Asia WGS AF: 0.107 AC: 372 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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	11202+7C>A in intron 68 of DNAH11: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus se quence. It has been identified in 28.2% (1011/3586) of African American chromoso mes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs .washington.edu/EVS; dbSNP rs73279826). -

Primary ciliary dyskinesia Benign:2

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

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.99
Dann	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00010
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs73279826; hg19: chr7-21894080; COSMIC: COSV60946520;