rs73279830

Positions:

• chr7-21854468-G-A

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+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0698 in 1,609,544 control chromosomes in the GnomAD database, including 8,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2625 hom., cov: 32)
  • Exomes 𝑓: 0.063 (5388 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.334

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=-0.93).
• BP6: Variant 7-21854468-G-A is Benign according to our data. Variant chr7-21854468-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 163124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21854468-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.11202+13G>A		intron_variant		ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.11202+13G>A		intron_variant		5	NM_001277115.2	ENSP00000475939	P1
DNAH11	ENST00000421290.1	n.385+13G>A		intron_variant, non_coding_transcript_variant		4
DNAH11	ENST00000607413.5	n.465+13G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20711 AN: 151904 Hom.: 2621 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0465

Gnomad EAS AF: 0.228

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0628

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0439

Gnomad OTH AF: 0.114

GnomAD3 exomes AF: 0.0911 AC: 22470 AN: 246594 Hom.: 1885 AF XY: 0.0896 AC XY: 11978 AN XY: 133668

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.0425

Gnomad ASJ exome AF: 0.0494

Gnomad EAS exome AF: 0.227

Gnomad SAS exome AF: 0.139

Gnomad FIN exome AF: 0.0646

Gnomad NFE exome AF: 0.0480

Gnomad OTH exome AF: 0.0743

GnomAD4 exome AF: 0.0629 AC: 91644 AN: 1457522 Hom.: 5388 Cov.: 34 AF XY: 0.0642 AC XY: 46509 AN XY: 724790

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.0442

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.135

Gnomad4 FIN exome AF: 0.0610

Gnomad4 NFE exome AF: 0.0435

Gnomad4 OTH exome AF: 0.0853

GnomAD4 genome AF: 0.137 AC: 20754 AN: 152022 Hom.: 2625 Cov.: 32 AF XY: 0.138 AC XY: 10223 AN XY: 74334

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.0465

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0628

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0749 Hom.: 264

Bravo AF: 0.144

Asia WGS AF: 0.214 AC: 744 AN: 3478

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	11202+13G>A in intron 68 of DNAH11: This variant is not expected to have clinica l significance because it is not located within the conserved splice consensus s equence. It has been identified in 32.3% (1157/3584) of African American chromos omes from a broad population by the NHLBI Exome Sequencing Project (http://evs.g s.washington.edu/EVS; dbSNP rs73279830). -

Primary ciliary dyskinesia Benign:2

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

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
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs73279830; hg19: chr7-21894086; COSMIC: COSV60946538;