Variant rs7570005 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_001370.2(DNAH6):c.4611C>T(p.Ile1537=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 1,548,974 control chromosomes in the GnomAD database, including 12,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 4512 hom., cov: 32)

Exomes 𝑓: 0.086 ( 7726 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.92

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=-0.51).

BP6

Variant 2-84634599-C-T is Benign according to our data. Variant chr2-84634599-C-T is described in ClinVar as [Benign]. Clinvar id is 402737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH6	NM_001370.2 linkuse as main transcript	c.4611C>T	p.Ile1537=	synonymous_variant	30/77	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.4611C>T	p.Ile1537=	synonymous_variant	30/77	5	NM_001370.2	ENSP00000374045	P1	Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27021

AN:

152094

Hom.:

4496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.437

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0508

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.0778

Gnomad OTH

AF:

0.157

GnomAD3 exomes

AF:

0.0899

AC:

13865

AN:

154154

Hom.:

1193

AF XY:

0.0873

AC XY:

7127

AN XY:

81658

show subpopulations

Gnomad AFR exome

AF:

0.440

Gnomad AMR exome

AF:

0.0688

Gnomad ASJ exome

AF:

0.0622

Gnomad EAS exome

AF:

0.00945

Gnomad SAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.0474

Gnomad NFE exome

AF:

0.0770

Gnomad OTH exome

AF:

0.0855

GnomAD4 exome

AF:

0.0861

AC:

120316

AN:

1396762

Hom.:

7726

Cov.:

AF XY:

0.0861

AC XY:

59299

AN XY:

688872

show subpopulations

Gnomad4 AFR exome

AF:

0.444

Gnomad4 AMR exome

AF:

0.0751

Gnomad4 ASJ exome

AF:

0.0621

Gnomad4 EAS exome

AF:

0.0219

Gnomad4 SAS exome

AF:

0.109

Gnomad4 FIN exome

AF:

0.0467

Gnomad4 NFE exome

AF:

0.0777

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.178

AC:

27083

AN:

152212

Hom.:

4512

Cov.:

AF XY:

0.174

AC XY:

12961

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.437

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0605

Gnomad4 EAS

AF:

0.0133

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.0508

Gnomad4 NFE

AF:

0.0778

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.120

Hom.:

1096

Bravo

AF:

0.192

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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, no assertion criteria provided

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.2

DANN

Benign

0.69

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