rs35982798

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015512.5(DNAH1):c.2430C>T(p.Thr810Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,613,948 control chromosomes in the GnomAD database, including 1,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T810T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.035 ( 134 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1529 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.32

Publications

7 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 -21 ACMG points.

BP4

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

BP6

Variant 3-52349324-C-T is Benign according to our data. Variant chr3-52349324-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.32 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0345 (5256/152268) while in subpopulation NFE AF = 0.0465 (3161/68010). AF 95% confidence interval is 0.0451. There are 134 homozygotes in GnomAd4. There are 2417 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 134 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.2430C>T	p.Thr810Thr	synonymous_variant	Exon 14 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.2430C>T	p.Thr810Thr	synonymous_variant	Exon 15 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.2430C>T	p.Thr810Thr	synonymous_variant	Exon 15 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.2430C>T	p.Thr810Thr	synonymous_variant	Exon 15 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 link	c.2430C>T	p.Thr810Thr	synonymous_variant	Exon 14 of 78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.2691C>T		non_coding_transcript_exon_variant	Exon 14 of 77	2
DNAH1	ENST00000497875.1 link	n.2595C>T		non_coding_transcript_exon_variant	Exon 15 of 21	2

Frequencies

GnomAD3 genomes

AF:

0.0345

AC:

5255

AN:

152150

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0137

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0461

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.0218

Gnomad SAS

AF:

0.0222

Gnomad FIN

AF:

0.0305

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0465

Gnomad OTH

AF:

0.0416

GnomAD2 exomes

AF:

0.0354

AC:

8821

AN:

249214

AF XY:

0.0357

show subpopulations

Gnomad AFR exome

AF:

0.0141

Gnomad AMR exome

AF:

0.0339

Gnomad ASJ exome

AF:

0.0276

Gnomad EAS exome

AF:

0.0180

Gnomad FIN exome

AF:

0.0326

Gnomad NFE exome

AF:

0.0465

Gnomad OTH exome

AF:

0.0453

GnomAD4 exome

AF:

0.0431

AC:

63040

AN:

1461680

Hom.:

1529

Cov.:

AF XY:

0.0428

AC XY:

31101

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.0143

AC:

478

AN:

33480

American (AMR)

AF:

0.0363

AC:

1625

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0283

AC:

739

AN:

26136

East Asian (EAS)

AF:

0.0167

AC:

663

AN:

39700

South Asian (SAS)

AF:

0.0201

AC:

1734

AN:

86258

European-Finnish (FIN)

AF:

0.0335

AC:

1787

AN:

53378

Middle Eastern (MID)

AF:

0.0361

AC:

208

AN:

5768

European-Non Finnish (NFE)

AF:

0.0478

AC:

53119

AN:

1111864

Other (OTH)

AF:

0.0445

AC:

2687

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

3807

7614

11420

15227

19034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1950

3900

5850

7800

9750

<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:

0.0345

AC:

5256

AN:

152268

Hom.:

134

Cov.:

AF XY:

0.0325

AC XY:

2417

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0136

AC:

566

AN:

41558

American (AMR)

AF:

0.0460

AC:

704

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3472

East Asian (EAS)

AF:

0.0214

AC:

111

AN:

5176

South Asian (SAS)

AF:

0.0220

AC:

106

AN:

4826

European-Finnish (FIN)

AF:

0.0305

AC:

324

AN:

10610

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0465

AC:

3161

AN:

68010

Other (OTH)

AF:

0.0435

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

246

493

739

986

1232

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0412

Hom.:

Bravo

AF:

0.0355

Asia WGS

AF:

0.0360

AC:

124

AN:

3478

EpiCase

AF:

0.0479

EpiControl

AF:

0.0519

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.052

(source)

DANN

Benign

0.47

PhyloP100

-5.3

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over