Genetic Variant DNAH6:c.400-22_400-21dupTT (chr2-84528872-A-ATT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001370.2(DNAH6):c.400-22_400-21dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.24 ( 5262 hom., cov: 0)

Exomes 𝑓: 0.34 ( 16393 hom. )

Failed GnomAD Quality Control

Consequence

DNAH6
NM_001370.2 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.797

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 2-84528872-A-ATT is Benign according to our data. Variant chr2-84528872-A-ATT is described in ClinVar as [Benign]. Clinvar id is 1271750.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.400-22_400-21dupTT		intron_variant	Intron 3 of 76	ENST00000389394.8	NP_001361.1	Q9C0G6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH6	ENST00000389394.8 link	c.400-32_400-31insTT	intron_variant	Intron 3 of 76	5	NM_001370.2	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1 link	n.229+10821_229+10822insTT	intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1 link	n.454+3134_454+3135insTT	intron_variant	Intron 3 of 3	4
DNAH6	ENST00000476689.5 link	n.536+3134_536+3135insTT	intron_variant	Intron 3 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

36274

AN:

148274

Hom.:

5261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.237

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.165

Gnomad SAS

AF:

0.235

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.179

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.230

GnomAD2 exomes

AF:

0.326

AC:

29680

AN:

91098

AF XY:

0.330

show subpopulations

Gnomad AFR exome

AF:

0.185

Gnomad AMR exome

AF:

0.298

Gnomad ASJ exome

AF:

0.341

Gnomad EAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.346

Gnomad OTH exome

AF:

0.327

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.343

AC:

374217

AN:

1091380

Hom.:

16393

Cov.:

AF XY:

0.343

AC XY:

183598

AN XY:

535828

show subpopulations

African (AFR)

AF:

0.166

AC:

3522

AN:

21204

American (AMR)

AF:

0.294

AC:

5829

AN:

19812

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

5935

AN:

17972

East Asian (EAS)

AF:

0.269

AC:

6169

AN:

22946

South Asian (SAS)

AF:

0.312

AC:

17849

AN:

57278

European-Finnish (FIN)

AF:

0.365

AC:

13844

AN:

37958

Middle Eastern (MID)

AF:

0.212

AC:

952

AN:

4482

European-Non Finnish (NFE)

AF:

0.354

AC:

306019

AN:

865662

Other (OTH)

AF:

0.320

AC:

14098

AN:

44066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

11856

23711

35567

47422

59278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.245

AC:

36284

AN:

148358

Hom.:

5262

Cov.:

AF XY:

0.243

AC XY:

17520

AN XY:

71966

show subpopulations

African (AFR)

AF:

0.105

AC:

4221

AN:

40354

American (AMR)

AF:

0.237

AC:

3537

AN:

14910

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

863

AN:

3454

East Asian (EAS)

AF:

0.165

AC:

827

AN:

5022

South Asian (SAS)

AF:

0.236

AC:

1093

AN:

4632

European-Finnish (FIN)

AF:

0.333

AC:

3133

AN:

9416

Middle Eastern (MID)

AF:

0.188

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.322

AC:

21701

AN:

67302

Other (OTH)

AF:

0.231

AC:

478

AN:

2070

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1207

2413

3620

4826

6033

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.329

Hom.:

396

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 12, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.80

La Branchor

0.96

BranchPoint Hunter

6.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-84528872-A-ATT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over