Genetic Variant DNAH6:c.400-21delT (chr2-84528872-AT-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001370.2(DNAH6):c.400-21delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000141 in 1,328,752 control chromosomes in the GnomAD database, including 1 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 0.00052 ( 1 hom., cov: 0)

Exomes 𝑓: 0.000093 ( 0 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):

spermatogenic failure
Inheritance: AR Classification: STRONG Submitted by: ClinGen
male infertility with azoospermia or oligozoospermia due to single gene mutation
Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
primary ciliary dyskinesia
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

DNAH6 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH6	NM_001370.2	MANE Select	c.400-21delT		intron	N/A	NP_001361.1	Q9C0G6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAH6	ENST00000389394.8	TSL:5 MANE Select	c.400-31delT	intron	N/A	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1	TSL:1	n.229+10822delT	intron	N/A
DNAH6	ENST00000468661.1	TSL:4	n.454+3135delT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000518

AC:

AN:

148522

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000268

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00146

GnomAD2 exomes

AF:

0.000252

AC:

AN:

91098

AF XY:

0.000249

show subpopulations

Gnomad AFR exome

AF:

0.00220

Gnomad AMR exome

AF:

0.0000857

Gnomad ASJ exome

AF:

0.000418

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000899

Gnomad NFE exome

AF:

0.000155

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000932

AC:

110

AN:

1180144

Hom.:

Cov.:

AF XY:

0.0000828

AC XY:

AN XY:

579532

show subpopulations

African (AFR)

AF:

0.00252

AC:

AN:

24164

American (AMR)

AF:

0.0000918

AC:

AN:

21798

Ashkenazi Jewish (ASJ)

AF:

0.0000503

AC:

AN:

19892

East Asian (EAS)

AF:

0.00

AC:

AN:

27970

South Asian (SAS)

AF:

0.000113

AC:

AN:

61690

European-Finnish (FIN)

AF:

0.0000492

AC:

AN:

40672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4796

European-Non Finnish (NFE)

AF:

0.0000312

AC:

AN:

930838

Other (OTH)

AF:

0.000166

AC:

AN:

48324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000525

AC:

AN:

148608

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

72122

show subpopulations

African (AFR)

AF:

0.00176

AC:

AN:

40404

American (AMR)

AF:

0.000268

AC:

AN:

14938

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5030

South Asian (SAS)

AF:

0.00

AC:

AN:

4636

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9498

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67376

Other (OTH)

AF:

0.00145

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.80

La Branchor

0.96

BranchPoint Hunter

6.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

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2-84528872-ATTT-ATT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over