rs17144747

Positions:

• chr7-21599954-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.2835A>G​(p.Gln945=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,613,536 control chromosomes in the GnomAD database, including 2,471 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (516 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1955 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.12

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-21599954-A-G is Benign according to our data. Variant chr7-21599954-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 93685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21599954-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.2835A>G	p.Gln945=	synonymous_variant	15/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.2835A>G	p.Gln945=	synonymous_variant	15/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10500 AN: 152072 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0198

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0349

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0453

Gnomad OTH AF: 0.0593

GnomAD3 exomes AF: 0.0469 AC: 11660 AN: 248418 Hom.: 390 AF XY: 0.0467 AC XY: 6295 AN XY: 134766

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0485

Gnomad EAS exome AF: 0.0267

Gnomad SAS exome AF: 0.0548

Gnomad FIN exome AF: 0.0345

Gnomad NFE exome AF: 0.0460

Gnomad OTH exome AF: 0.0413

GnomAD4 exome AF: 0.0467 AC: 68309 AN: 1461346 Hom.: 1955 Cov.: 32 AF XY: 0.0467 AC XY: 33936 AN XY: 726936

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.0461

Gnomad4 EAS exome AF: 0.0154

Gnomad4 SAS exome AF: 0.0564

Gnomad4 FIN exome AF: 0.0365

Gnomad4 NFE exome AF: 0.0454

Gnomad4 OTH exome AF: 0.0517

GnomAD4 genome AF: 0.0692 AC: 10527 AN: 152190 Hom.: 516 Cov.: 32 AF XY: 0.0673 AC XY: 5009 AN XY: 74430

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0358

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.0199

Gnomad4 SAS AF: 0.0622

Gnomad4 FIN AF: 0.0349

Gnomad4 NFE AF: 0.0453

Gnomad4 OTH AF: 0.0587

Alfa AF: 0.0521 Hom.: 359

Bravo AF: 0.0722

Asia WGS AF: 0.0480 AC: 168 AN: 3478

EpiCase AF: 0.0417

EpiControl AF: 0.0419

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	Gln945Gln in exon 15 of DNAH11: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 12.2% (449/3690) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs17144747). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 05, 2015	- -

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	Invitae	Feb 01, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	12
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs17144747; hg19: chr7-21639572; COSMIC: COSV60985255;