chr3-52372379-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_015512.5(DNAH1):c.6819G>A(p.Leu2273Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00486 in 1,613,736 control chromosomes in the GnomAD database, including 607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 43 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 564 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.13

Publications

6 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 3-52372379-G-A is Benign according to our data. Variant chr3-52372379-G-A is described in ClinVar as Benign. ClinVar VariationId is 478482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.6819G>A	p.Leu2273Leu	synonymous_variant	Exon 43 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.6888G>A	p.Leu2296Leu	synonymous_variant	Exon 45 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.6819G>A	p.Leu2273Leu	synonymous_variant	Exon 44 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.6888G>A	p.Leu2296Leu	synonymous_variant	Exon 45 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 link	c.6819G>A	p.Leu2273Leu	synonymous_variant	Exon 43 of 78	1	NM_015512.5	ENSP00000401514.2		Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.7080G>A		non_coding_transcript_exon_variant	Exon 43 of 77	2

Frequencies

GnomAD3 genomes

AF:

0.00421

AC:

640

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00919

AC:

2288

AN:

248850

AF XY:

0.00892

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.00136

Gnomad NFE exome

AF:

0.000664

Gnomad OTH exome

AF:

0.00464

GnomAD4 exome

AF:

0.00492

AC:

7195

AN:

1461460

Hom.:

564

Cov.:

AF XY:

0.00486

AC XY:

3536

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.162

AC:

6417

AN:

39698

South Asian (SAS)

AF:

0.00195

AC:

168

AN:

86256

European-Finnish (FIN)

AF:

0.00128

AC:

AN:

53174

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000228

AC:

254

AN:

1111856

Other (OTH)

AF:

0.00454

AC:

274

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

349

699

1048

1398

1747

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.00421

AC:

641

AN:

152276

Hom.:

Cov.:

AF XY:

0.00477

AC XY:

355

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41550

American (AMR)

AF:

0.000719

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.112

AC:

579

AN:

5164

South Asian (SAS)

AF:

0.00373

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000942

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68028

Other (OTH)

AF:

0.00331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

119

149

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.000596

Hom.:

Bravo

AF:

0.00437

Asia WGS

AF:

0.0390

AC:

135

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 09, 2020

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

Jan 23, 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

-0.43

CADD

Benign

6.4

(source)

DANN

Benign

0.76

PhyloP100

4.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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