rs11768670

Positions:

• chr7-21725879-G-A
• chr7-21725879-G-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.7335G>A​(p.Ser2445=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,607,404 control chromosomes in the GnomAD database, including 40,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3233 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37286 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.613

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 7-21725879-G-A is Benign according to our data. Variant chr7-21725879-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 178728.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21725879-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.613 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.7335G>A	p.Ser2445=	synonymous_variant	45/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.7335G>A	p.Ser2445=	synonymous_variant	45/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29924 AN: 151894 Hom.: 3233 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.0963

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.189 AC: 45161 AN: 238888 Hom.: 4745 AF XY: 0.190 AC XY: 24439 AN XY: 128966

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.135

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.0521

Gnomad SAS exome AF: 0.102

Gnomad FIN exome AF: 0.270

Gnomad NFE exome AF: 0.240

Gnomad OTH exome AF: 0.206

GnomAD4 exome AF: 0.221 AC: 321286 AN: 1455392 Hom.: 37286 Cov.: 37 AF XY: 0.218 AC XY: 157476 AN XY: 723162

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.0704

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.269

Gnomad4 NFE exome AF: 0.240

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.197 AC: 29926 AN: 152012 Hom.: 3233 Cov.: 32 AF XY: 0.195 AC XY: 14484 AN XY: 74284

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0567

Gnomad4 SAS AF: 0.0961

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.193

Alfa AF: 0.218 Hom.: 8390

Bravo AF: 0.189

Asia WGS AF: 0.0830 AC: 290 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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Ser2445Ser in exon 45 of DNAH11: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 23.6% (1930/8180) of European American chromosomes from a broad population by the NHLBI Exome Seq uencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11768670). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	Nov 10, 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	-0.32
CADD	Benign	8.3
DANN	Benign	0.75

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: rs11768670; hg19: chr7-21765497; COSMIC: COSV60955953;