Variant 2-84573481-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001370.2(DNAH6):c.1818C>A(p.Ala606Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 1,577,730 control chromosomes in the GnomAD database, including 703,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64798 hom., cov: 33)

Exomes 𝑓: 0.95 ( 639149 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.364

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:

DNAH6 (HGNC:):

DNAH6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 2-84573481-C-A is Benign according to our data. Variant chr2-84573481-C-A is described in ClinVar as [Benign]. Clinvar id is 402734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.364 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.1818C>A	p.Ala606Ala	synonymous_variant	12/77	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.1818C>A	p.Ala606Ala	synonymous_variant	12/77	5	NM_001370.2	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1 linkuse as main transcript	n.861C>A		non_coding_transcript_exon_variant	6/9	1
DNAH6	ENST00000476689.5 linkuse as main transcript	n.1168C>A		non_coding_transcript_exon_variant	8/11	2

Frequencies

GnomAD3 genomes

AF:

0.921

AC:

140152

AN:

152160

Hom.:

64767

Cov.:

show subpopulations

Gnomad AFR

AF:

0.840

Gnomad AMI

AF:

0.916

Gnomad AMR

AF:

0.950

Gnomad ASJ

AF:

0.984

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.950

Gnomad FIN

AF:

0.959

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.947

Gnomad OTH

AF:

0.936

GnomAD3 exomes

AF:

0.949

AC:

206970

AN:

218172

Hom.:

98319

AF XY:

0.951

AC XY:

112904

AN XY:

118734

show subpopulations

Gnomad AFR exome

AF:

0.830

Gnomad AMR exome

AF:

0.969

Gnomad ASJ exome

AF:

0.985

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.951

Gnomad FIN exome

AF:

0.963

Gnomad NFE exome

AF:

0.947

Gnomad OTH exome

AF:

0.952

GnomAD4 exome

AF:

0.947

AC:

1349390

AN:

1425452

Hom.:

639149

Cov.:

AF XY:

0.947

AC XY:

671555

AN XY:

708898

show subpopulations

Gnomad4 AFR exome

AF:

0.830

Gnomad4 AMR exome

AF:

0.967

Gnomad4 ASJ exome

AF:

0.985

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.952

Gnomad4 FIN exome

AF:

0.962

Gnomad4 NFE exome

AF:

0.946

Gnomad4 OTH exome

AF:

0.944

GnomAD4 genome

AF:

0.921

AC:

140239

AN:

152278

Hom.:

64798

Cov.:

AF XY:

0.923

AC XY:

68701

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.839

Gnomad4 AMR

AF:

0.950

Gnomad4 ASJ

AF:

0.984

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.950

Gnomad4 FIN

AF:

0.959

Gnomad4 NFE

AF:

0.947

Gnomad4 OTH

AF:

0.937

Alfa

AF:

0.944

Hom.:

81523

Bravo

AF:

0.918

Asia WGS

AF:

0.966

AC:

3361

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

3.9

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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