rs1192295

Variant summary

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

The NM_001370.2(DNAH6):c.7353A>G(p.Thr2451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0621 in 1,552,234 control chromosomes in the GnomAD database, including 4,495 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1343 hom., cov: 33)

Exomes 𝑓: 0.058 ( 3152 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.139

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=-0.61).

BP6

Variant 2-84694309-A-G is Benign according to our data. Variant chr2-84694309-A-G is described in ClinVar as [Benign]. Clinvar id is 402741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.139 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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.7353A>G	p.Thr2451=	synonymous_variant	46/77	ENST00000389394.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.7353A>G	p.Thr2451=	synonymous_variant	46/77	5	NM_001370.2	P1	Q9C0G6-1
DNAH6	ENST00000602588.1 linkuse as main transcript	n.1434A>G		non_coding_transcript_exon_variant	10/11	1

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15521

AN:

152206

Hom.:

1342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0593

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.0610

Gnomad FIN

AF:

0.0409

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0556

Gnomad OTH

AF:

0.0812

GnomAD3 exomes

AF:

0.0553

AC:

8768

AN:

158578

Hom.:

429

AF XY:

0.0530

AC XY:

4430

AN XY:

83574

show subpopulations

Gnomad AFR exome

AF:

0.241

Gnomad AMR exome

AF:

0.0343

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.00128

Gnomad SAS exome

AF:

0.0649

Gnomad FIN exome

AF:

0.0381

Gnomad NFE exome

AF:

0.0546

Gnomad OTH exome

AF:

0.0515

GnomAD4 exome

AF:

0.0578

AC:

80911

AN:

1399910

Hom.:

3152

Cov.:

AF XY:

0.0573

AC XY:

39574

AN XY:

690446

show subpopulations

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.0376

Gnomad4 ASJ exome

AF:

0.0192

Gnomad4 EAS exome

AF:

0.000811

Gnomad4 SAS exome

AF:

0.0644

Gnomad4 FIN exome

AF:

0.0386

Gnomad4 NFE exome

AF:

0.0560

Gnomad4 OTH exome

AF:

0.0637

GnomAD4 genome

AF:

0.102

AC:

15544

AN:

152324

Hom.:

1343

Cov.:

AF XY:

0.0994

AC XY:

7401

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.0592

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0613

Gnomad4 FIN

AF:

0.0409

Gnomad4 NFE

AF:

0.0556

Gnomad4 OTH

AF:

0.0803

Alfa

AF:

0.0604

Hom.:

963

Bravo

AF:

0.107

Asia WGS

AF:

0.0460

AC:

162

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: MAF -

DNAH6-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 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

-0.61

Cadd

Benign

3.1

Dann

Benign

0.66

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