rs746239

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015512.5(DNAH1):c.6139-15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,613,830 control chromosomes in the GnomAD database, including 10,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 631 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10236 hom. )

Consequence

DNAH1
NM_015512.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.325

Publications

11 publications found

Variant links:

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

DNAH1 Gene-Disease associations (from GenCC):

spermatogenic failure 18
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
ciliary dyskinesia, primary, 37
Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
non-syndromic male infertility due to sperm motility disorder
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DNAH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-52370095-G-A is Benign according to our data. Variant chr3-52370095-G-A is described in ClinVar as Benign. ClinVar VariationId is 402600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
DNAH1	NM_015512.5 link	c.6139-15G>A	intron_variant	Intron 38 of 77	ENST00000420323.7	NP_056327.4
DNAH1	XM_017006129.2 link	c.6208-15G>A	intron_variant	Intron 40 of 79		XP_016861618.1
DNAH1	XM_017006130.2 link	c.6139-15G>A	intron_variant	Intron 39 of 78		XP_016861619.1
DNAH1	XM_017006131.2 link	c.6208-15G>A	intron_variant	Intron 40 of 78		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 link	c.6139-15G>A		intron_variant	Intron 38 of 77	1	NM_015512.5	ENSP00000401514.2
DNAH1	ENST00000486752.5 link	n.6400-15G>A		intron_variant	Intron 38 of 76	2

Frequencies

GnomAD3 genomes

AF:

0.0822

AC:

12504

AN:

152170

Hom.:

632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0354

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0753

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0658

Gnomad FIN

AF:

0.0527

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.104

GnomAD2 exomes

AF:

0.0851

AC:

21189

AN:

248960

AF XY:

0.0861

show subpopulations

Gnomad AFR exome

AF:

0.0350

Gnomad AMR exome

AF:

0.0642

Gnomad ASJ exome

AF:

0.120

Gnomad EAS exome

AF:

0.000223

Gnomad FIN exome

AF:

0.0564

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0933

GnomAD4 exome

AF:

0.113

AC:

164725

AN:

1461542

Hom.:

10236

Cov.:

AF XY:

0.111

AC XY:

81007

AN XY:

727068

show subpopulations

African (AFR)

AF:

0.0371

AC:

1242

AN:

33478

American (AMR)

AF:

0.0672

AC:

3005

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

3162

AN:

26130

East Asian (EAS)

AF:

0.000302

AC:

AN:

39698

South Asian (SAS)

AF:

0.0751

AC:

6479

AN:

86254

European-Finnish (FIN)

AF:

0.0593

AC:

3163

AN:

53356

Middle Eastern (MID)

AF:

0.100

AC:

579

AN:

5768

European-Non Finnish (NFE)

AF:

0.126

AC:

140638

AN:

1111778

Other (OTH)

AF:

0.107

AC:

6445

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

9388

18775

28163

37550

46938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5062

10124

15186

20248

25310

<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:

0.0821

AC:

12505

AN:

152288

Hom.:

631

Cov.:

AF XY:

0.0791

AC XY:

5888

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0354

AC:

1471

AN:

41566

American (AMR)

AF:

0.0752

AC:

1150

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

440

AN:

3470

East Asian (EAS)

AF:

0.000771

AC:

AN:

5190

South Asian (SAS)

AF:

0.0665

AC:

321

AN:

4828

European-Finnish (FIN)

AF:

0.0527

AC:

560

AN:

10624

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.121

AC:

8245

AN:

67992

Other (OTH)

AF:

0.103

AC:

217

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

606

1212

1819

2425

3031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0991

Hom.:

162

Bravo

AF:

0.0812

Asia WGS

AF:

0.0280

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.64

(source)

DANN

Benign

0.75

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over