Variant rs78763603 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001277115.2(DNAH11):c.6117G>A(p.Ala2039=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00671 in 1,613,628 control chromosomes in the GnomAD database, including 842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0086 ( 110 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 732 hom. )

Consequence

DNAH11
NM_001277115.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -5.61

Variant links:

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]

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 7-21698150-G-A is Benign according to our data. Variant chr7-21698150-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 226587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.6117G>A	p.Ala2039=	synonymous_variant	36/82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.6117G>A	p.Ala2039=	synonymous_variant	36/82	5	NM_001277115.2	ENSP00000475939	P1

Frequencies

GnomAD3 genomes

AF:

0.00861

AC:

1310

AN:

152172

Hom.:

110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.201

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.00801

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.0179

AC:

4460

AN:

248952

Hom.:

411

AF XY:

0.0167

AC XY:

2250

AN XY:

135052

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.000495

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.00934

Gnomad NFE exome

AF:

0.000310

Gnomad OTH exome

AF:

0.00844

GnomAD4 exome

AF:

0.00651

AC:

9518

AN:

1461336

Hom.:

732

Cov.:

AF XY:

0.00656

AC XY:

4772

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000448

Gnomad4 ASJ exome

AF:

0.00103

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.0124

Gnomad4 FIN exome

AF:

0.00775

Gnomad4 NFE exome

AF:

0.000168

Gnomad4 OTH exome

AF:

0.0134

GnomAD4 genome

AF:

0.00858

AC:

1307

AN:

152292

Hom.:

110

Cov.:

AF XY:

0.00978

AC XY:

728

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.0149

Gnomad4 FIN

AF:

0.00801

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00838

Hom.:

206

Bravo

AF:

0.00981

Asia WGS

AF:

0.0740

AC:

257

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Ala2039Ala in exon 36 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 24.0% (48/200) of Han Chinese chromosomes from a broad population by the 1000 Genomes Project (ht tp://www.ncbi.nlm.nih.gov/projects/SNP; dbSNP rs78763603). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 26, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0030

DANN

Benign

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over