dbSNP rs1192269: DNAH6:p.Val2898Ile (chr2-84705712-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001370.2(DNAH6):c.8692G>A(p.Val2898Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0491 in 1,550,596 control chromosomes in the GnomAD database, including 2,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 153 hom., cov: 32)

Exomes 𝑓: 0.050 ( 2017 hom. )

Consequence

DNAH6
NM_001370.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.17

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0039929748).

BP6

Variant 2-84705712-G-A is Benign according to our data. Variant chr2-84705712-G-A is described in ClinVar as [Benign]. Clinvar id is 402743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.8692G>A	p.Val2898Ile	missense_variant	Exon 52 of 77	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8 link	c.8692G>A	p.Val2898Ile	missense_variant	Exon 52 of 77	5	NM_001370.2	ENSP00000374045.3		Q9C0G6-1

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5804

AN:

152060

Hom.:

153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0181

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.0315

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.0613

Gnomad FIN

AF:

0.0408

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0533

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0403

AC:

6304

AN:

156304

Hom.:

168

AF XY:

0.0418

AC XY:

3449

AN XY:

82608

show subpopulations

Gnomad AFR exome

AF:

0.0181

Gnomad AMR exome

AF:

0.0208

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.0646

Gnomad FIN exome

AF:

0.0380

Gnomad NFE exome

AF:

0.0530

Gnomad OTH exome

AF:

0.0415

GnomAD4 exome

AF:

0.0503

AC:

70338

AN:

1398418

Hom.:

2017

Cov.:

AF XY:

0.0507

AC XY:

34950

AN XY:

689714

show subpopulations

Gnomad4 AFR exome

AF:

0.0172

Gnomad4 AMR exome

AF:

0.0215

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.000784

Gnomad4 SAS exome

AF:

0.0639

Gnomad4 FIN exome

AF:

0.0387

Gnomad4 NFE exome

AF:

0.0545

Gnomad4 OTH exome

AF:

0.0459

GnomAD4 genome

AF:

0.0381

AC:

5803

AN:

152178

Hom.:

153

Cov.:

AF XY:

0.0378

AC XY:

2810

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0180

Gnomad4 AMR

AF:

0.0315

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00212

Gnomad4 SAS

AF:

0.0616

Gnomad4 FIN

AF:

0.0408

Gnomad4 NFE

AF:

0.0533

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0469

Hom.:

312

Bravo

AF:

0.0353

TwinsUK

AF:

0.0547

AC:

203

ALSPAC

AF:

0.0506

AC:

195

ESP6500AA

AF:

0.0210

AC:

ESP6500EA

AF:

0.0515

AC:

164

ExAC

AF:

0.0431

AC:

1076

Asia WGS

AF:

0.0310

AC:

107

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

T;T

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

D;.

MetaRNN

Benign

0.0040

T;T

MetaSVM

Uncertain

-0.16

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.92

N;N

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.16

MPC

0.38

ClinPred

0.017

GERP RS

6.0

Varity_R

0.33

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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