dbSNP rs67469465: DNAH6:c.400-23_400-21delTTT (chr2-84528872-ATTT-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001370.2(DNAH6):c.400-23_400-21delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,329,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000067 ( 0 hom., cov: 0)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

DNAH6
NM_001370.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.400-23_400-21delTTT		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.400-31_400-29delTTT	intron	N/A	ENSP00000374045.3	Q9C0G6-1
DNAH6	ENST00000494025.1	TSL:1	n.229+10822_229+10824delTTT	intron	N/A
DNAH6	ENST00000468661.1	TSL:4	n.454+3135_454+3137delTTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148528

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

8.47e-7

AC:

AN:

1180760

Hom.:

AF XY:

0.00

AC XY:

AN XY:

579846

show subpopulations

African (AFR)

AF:

0.0000413

AC:

AN:

24208

American (AMR)

AF:

0.00

AC:

AN:

21838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19894

East Asian (EAS)

AF:

0.00

AC:

AN:

27986

South Asian (SAS)

AF:

0.00

AC:

AN:

61752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40684

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4796

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

931246

Other (OTH)

AF:

0.00

AC:

AN:

48356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000673

AC:

AN:

148528

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

72028

show subpopulations

African (AFR)

AF:

0.0000248

AC:

AN:

40292

American (AMR)

AF:

0.00

AC:

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5042

South Asian (SAS)

AF:

0.00

AC:

AN:

4654

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9500

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67386

Other (OTH)

AF:

0.00

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.31

La Branchor

0.96

BranchPoint Hunter

6.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over