rs729657

chr7-21744419-C-T

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.8155-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0815 in 1,609,344 control chromosomes in the GnomAD database, including 6,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (338 hom., cov: 33)
  • Exomes 𝑓: 0.084 (5674 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.211

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=-0.75).
• BP6: Variant 7-21744419-C-T is Benign according to our data. Variant chr7-21744419-C-T is described in ClinVar as [Benign]. Clinvar id is 257934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21744419-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.8155-19C>T		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.8155-19C>T		intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000605912.1	c.475-451C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0563 AC: 8567 AN: 152068 Hom.: 336 Cov.: 33

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0684

Gnomad FIN AF: 0.0644

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0527

GnomAD3 exomes AF: 0.0652 AC: 16015 AN: 245636 Hom.: 673 AF XY: 0.0675 AC XY: 8988 AN XY: 133104

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.0478

Gnomad ASJ exome AF: 0.0431

Gnomad EAS exome AF: 0.00174

Gnomad SAS exome AF: 0.0763

Gnomad FIN exome AF: 0.0656

Gnomad NFE exome AF: 0.0863

Gnomad OTH exome AF: 0.0681

GnomAD4 exome AF: 0.0841 AC: 122612 AN: 1457156 Hom.: 5674 Cov.: 31 AF XY: 0.0838 AC XY: 60693 AN XY: 724598

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0481

Gnomad4 ASJ exome AF: 0.0460

Gnomad4 EAS exome AF: 0.000933

Gnomad4 SAS exome AF: 0.0781

Gnomad4 FIN exome AF: 0.0663

Gnomad4 NFE exome AF: 0.0934

Gnomad4 OTH exome AF: 0.0764

GnomAD4 genome AF: 0.0563 AC: 8569 AN: 152188 Hom.: 338 Cov.: 33 AF XY: 0.0550 AC XY: 4093 AN XY: 74404

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0434

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0682

Gnomad4 FIN AF: 0.0644

Gnomad4 NFE AF: 0.0870

Gnomad4 OTH AF: 0.0522

Alfa AF: 0.0792 Hom.: 283

Bravo AF: 0.0524

Asia WGS AF: 0.0280 AC: 96 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	9.1
Dann	Benign	0.62

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: rs729657; hg19: chr7-21784037;