Variant rs1192344 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.9753G>A(p.Leu3251Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 1,545,136 control chromosomes in the GnomAD database, including 2,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 522 hom., cov: 32)

Exomes 𝑓: 0.055 ( 2430 hom. )

Consequence

DNAH6
NM_001370.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.510

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 2-84718345-G-A is Benign according to our data. Variant chr2-84718345-G-A is described in ClinVar as [Benign]. Clinvar id is 402744.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 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.9753G>A	p.Leu3251Leu	synonymous_variant	59/77	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8 linkuse as main transcript	c.9753G>A	p.Leu3251Leu	synonymous_variant	59/77	5	NM_001370.2	ENSP00000374045.3		Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

10817

AN:

152094

Hom.:

517

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0474

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.00211

Gnomad SAS

AF:

0.0612

Gnomad FIN

AF:

0.0407

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0552

Gnomad OTH

AF:

0.0608

GnomAD3 exomes

AF:

0.0491

AC:

7365

AN:

149880

Hom.:

246

AF XY:

0.0491

AC XY:

3887

AN XY:

79184

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.0306

Gnomad ASJ exome

AF:

0.0204

Gnomad EAS exome

AF:

0.00124

Gnomad SAS exome

AF:

0.0669

Gnomad FIN exome

AF:

0.0384

Gnomad NFE exome

AF:

0.0547

Gnomad OTH exome

AF:

0.0505

GnomAD4 exome

AF:

0.0546

AC:

76112

AN:

1392924

Hom.:

2430

Cov.:

AF XY:

0.0546

AC XY:

37527

AN XY:

686726

show subpopulations

Gnomad4 AFR exome

AF:

0.128

Gnomad4 AMR exome

AF:

0.0329

Gnomad4 ASJ exome

AF:

0.0194

Gnomad4 EAS exome

AF:

0.000814

Gnomad4 SAS exome

AF:

0.0644

Gnomad4 FIN exome

AF:

0.0386

Gnomad4 NFE exome

AF:

0.0557

Gnomad4 OTH exome

AF:

0.0573

GnomAD4 genome

AF:

0.0712

AC:

10839

AN:

152212

Hom.:

522

Cov.:

AF XY:

0.0701

AC XY:

5214

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0473

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0615

Gnomad4 FIN

AF:

0.0407

Gnomad4 NFE

AF:

0.0552

Gnomad4 OTH

AF:

0.0602

Alfa

AF:

0.0582

Hom.:

211

Bravo

AF:

0.0715

Asia WGS

AF:

0.0410

AC:

143

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

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, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 03, 2020

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

-0.41

CADD

Benign

5.0

DANN

Benign

0.84

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