rs3827657

Positions:

• chr7-21601600-G-A
• chr7-21601600-G-C
• chr7-21601600-G-T

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.3630G>A​(p.Gln1210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,583,142 control chromosomes in the GnomAD database, including 521,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47148 hom., cov: 31)
  • Exomes 𝑓: 0.81 (474048 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.499

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=-0.79).
• BP6: Variant 7-21601600-G-A is Benign according to our data. Variant chr7-21601600-G-A is described in ClinVar as [Benign]. Clinvar id is 163102.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21601600-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.499 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.3630G>A	p.Gln1210=	synonymous_variant	18/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.3630G>A	p.Gln1210=	synonymous_variant	18/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119404 AN: 151952 Hom.: 47106 Cov.: 31

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.820

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.787

GnomAD3 exomes AF: 0.772 AC: 182139 AN: 235816 Hom.: 70830 AF XY: 0.774 AC XY: 98660 AN XY: 127534

Gnomad AFR exome AF: 0.732

Gnomad AMR exome AF: 0.649

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.792

Gnomad SAS exome AF: 0.686

Gnomad FIN exome AF: 0.826

Gnomad NFE exome AF: 0.830

Gnomad OTH exome AF: 0.781

GnomAD4 exome AF: 0.812 AC: 1162082 AN: 1431072 Hom.: 474048 Cov.: 43 AF XY: 0.808 AC XY: 570938 AN XY: 706308

Gnomad4 AFR exome AF: 0.724

Gnomad4 AMR exome AF: 0.657

Gnomad4 ASJ exome AF: 0.684

Gnomad4 EAS exome AF: 0.759

Gnomad4 SAS exome AF: 0.691

Gnomad4 FIN exome AF: 0.832

Gnomad4 NFE exome AF: 0.835

Gnomad4 OTH exome AF: 0.803

GnomAD4 genome AF: 0.786 AC: 119496 AN: 152070 Hom.: 47148 Cov.: 31 AF XY: 0.780 AC XY: 57984 AN XY: 74350

Gnomad4 AFR AF: 0.741

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.820

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.790

Alfa AF: 0.808 Hom.: 62335

Bravo AF: 0.776

Asia WGS AF: 0.798 AC: 2778 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Gln1210Gln in exon 18 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 25.3% (958/3782) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs3827657). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Primary ciliary dyskinesia Benign:2

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

Primary ciliary dyskinesia 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.47

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: rs3827657; hg19: chr7-21641218; COSMIC: COSV60946186;