rs1006244

Variant summary

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

The NM_001370.2(DNAH6):c.2547A>G(p.Gln849=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0404 in 1,550,324 control chromosomes in the GnomAD database, including 3,985 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1846 hom., cov: 32)

Exomes 𝑓: 0.034 ( 2139 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.318

Variant links:

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 2016]

DNAH6 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=-0.94).

BP6

Variant 2-84588891-A-G is Benign according to our data. Variant chr2-84588891-A-G is described in ClinVar as [Benign]. Clinvar id is 402735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.318 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH6	NM_001370.2 linkuse as main transcript	c.2547A>G	p.Gln849=	synonymous_variant	16/77	ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.2547A>G	p.Gln849=	synonymous_variant	16/77	5	NM_001370.2	P1	Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15688

AN:

152144

Hom.:

1845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0686

Gnomad ASJ

AF:

0.0481

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0985

GnomAD3 exomes

AF:

0.0456

AC:

7154

AN:

156774

Hom.:

460

AF XY:

0.0443

AC XY:

3668

AN XY:

82852

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.0399

Gnomad ASJ exome

AF:

0.0524

Gnomad EAS exome

AF:

0.00937

Gnomad SAS exome

AF:

0.0608

Gnomad FIN exome

AF:

0.00977

Gnomad NFE exome

AF:

0.0257

Gnomad OTH exome

AF:

0.0424

GnomAD4 exome

AF:

0.0335

AC:

46890

AN:

1398062

Hom.:

2139

Cov.:

AF XY:

0.0341

AC XY:

23542

AN XY:

689544

show subpopulations

Gnomad4 AFR exome

AF:

0.293

Gnomad4 AMR exome

AF:

0.0440

Gnomad4 ASJ exome

AF:

0.0518

Gnomad4 EAS exome

AF:

0.0210

Gnomad4 SAS exome

AF:

0.0626

Gnomad4 FIN exome

AF:

0.00859

Gnomad4 NFE exome

AF:

0.0235

Gnomad4 OTH exome

AF:

0.0502

GnomAD4 genome

AF:

0.103

AC:

15705

AN:

152262

Hom.:

1846

Cov.:

AF XY:

0.0998

AC XY:

7431

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.0685

Gnomad4 ASJ

AF:

0.0481

Gnomad4 EAS

AF:

0.0114

Gnomad4 SAS

AF:

0.0601

Gnomad4 FIN

AF:

0.0103

Gnomad4 NFE

AF:

0.0248

Gnomad4 OTH

AF:

0.0989

Alfa

AF:

0.0592

Hom.:

488

Bravo

AF:

0.114

Asia WGS

AF:

0.0540

AC:

188

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DNAH6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

Cadd

Benign

0.18

Dann

Benign

0.16

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