Genetic Variant DNAH6:c.400-23_400-21dupTTT (chr2-84528872-A-ATTT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001370.2(DNAH6):c.400-23_400-21dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,304,062 control chromosomes in the GnomAD database, including 244 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.027 ( 92 hom., cov: 0)

Exomes 𝑓: 0.047 ( 152 hom. )

Consequence

DNAH6
NM_001370.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.797

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

DNAH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2 link	c.400-23_400-21dupTTT		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_400-31insTTT	intron_variant	Intron 3 of 76	5	NM_001370.2	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1 link	n.229+10821_229+10822insTTT	intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1 link	n.454+3134_454+3135insTTT	intron_variant	Intron 3 of 3	4
DNAH6	ENST00000476689.5 link	n.536+3134_536+3135insTTT	intron_variant	Intron 3 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.0275

AC:

4078

AN:

148486

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00586

Gnomad AMI

AF:

0.00773

Gnomad AMR

AF:

0.0389

Gnomad ASJ

AF:

0.0344

Gnomad EAS

AF:

0.000595

Gnomad SAS

AF:

0.0585

Gnomad FIN

AF:

0.0290

Gnomad MID

AF:

0.0609

Gnomad NFE

AF:

0.0370

Gnomad OTH

AF:

0.0360

GnomAD2 exomes

AF:

0.0482

AC:

4391

AN:

91098

AF XY:

0.0527

show subpopulations

Gnomad AFR exome

AF:

0.00619

Gnomad AMR exome

AF:

0.0379

Gnomad ASJ exome

AF:

0.0540

Gnomad EAS exome

AF:

0.00791

Gnomad FIN exome

AF:

0.0476

Gnomad NFE exome

AF:

0.0532

Gnomad OTH exome

AF:

0.0475

GnomAD4 exome

AF:

0.0470

AC:

54357

AN:

1155490

Hom.:

152

Cov.:

AF XY:

0.0483

AC XY:

27415

AN XY:

567302

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00809

AC:

195

AN:

24096

American (AMR)

AF:

0.0330

AC:

711

AN:

21548

Ashkenazi Jewish (ASJ)

AF:

0.0482

AC:

941

AN:

19522

East Asian (EAS)

AF:

0.00353

AC:

AN:

27776

South Asian (SAS)

AF:

0.0749

AC:

4544

AN:

60654

European-Finnish (FIN)

AF:

0.0438

AC:

1742

AN:

39756

Middle Eastern (MID)

AF:

0.0757

AC:

360

AN:

4756

European-Non Finnish (NFE)

AF:

0.0480

AC:

43631

AN:

909894

Other (OTH)

AF:

0.0450

AC:

2135

AN:

47488

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.363

Heterozygous variant carriers

2247

4494

6740

8987

11234

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0274

AC:

4075

AN:

148572

Hom.:

Cov.:

AF XY:

0.0279

AC XY:

2012

AN XY:

72100

show subpopulations

African (AFR)

AF:

0.00584

AC:

236

AN:

40404

American (AMR)

AF:

0.0388

AC:

580

AN:

14936

Ashkenazi Jewish (ASJ)

AF:

0.0344

AC:

119

AN:

3456

East Asian (EAS)

AF:

0.000596

AC:

AN:

5030

South Asian (SAS)

AF:

0.0580

AC:

269

AN:

4634

European-Finnish (FIN)

AF:

0.0290

AC:

275

AN:

9488

Middle Eastern (MID)

AF:

0.0651

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0370

AC:

2493

AN:

67354

Other (OTH)

AF:

0.0357

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

166

332

499

665

831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0303

Hom.:

396

ClinVar

Not reported in ClinVar

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

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr2-84528872-A-ATTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over