rs57952953

chr7-21619936-A-ATTAAT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):c.4378-17_4378-16insATTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,559,650 control chromosomes in the GnomAD database, including 142,372 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15627 hom., cov: 0)
  • Exomes 𝑓: 0.42 (126745 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.774

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 -16 ACMG points.

• BP6: Variant 7-21619936-A-ATTAAT is Benign according to our data. Variant chr7-21619936-A-ATTAAT is described in ClinVar as [Likely_benign]. Clinvar id is 93688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.4378-17_4378-16insATTTA		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.4378-17_4378-16insATTTA		intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000465593.1	n.404-17_404-16insATTTA		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67579 AN: 151354 Hom.: 15616 Cov.: 0

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.425

GnomAD3 exomes AF: 0.407 AC: 88438 AN: 217250 Hom.: 19085 AF XY: 0.407 AC XY: 48180 AN XY: 118288

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.735

Gnomad SAS exome AF: 0.379

Gnomad FIN exome AF: 0.379

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.417 AC: 587654 AN: 1408178 Hom.: 126745 Cov.: 30 AF XY: 0.416 AC XY: 291293 AN XY: 700296

Gnomad4 AFR exome AF: 0.496

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.339

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.389

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.446 AC: 67631 AN: 151472 Hom.: 15627 Cov.: 0 AF XY: 0.444 AC XY: 32884 AN XY: 73988

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.425

Alfa AF: 0.411 Hom.: 2196

Asia WGS AF: 0.564 AC: 1962 AN: 3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 12, 2015	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57952953; hg19: chr7-21659554;