rs374941590

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.732A>G(p.Pro244Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000943 in 1,612,050 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 3 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.66

Publications

0 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=-0.6).

BP6

Variant 3-52326885-A-G is Benign according to our data. Variant chr3-52326885-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 544651.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.66 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0000959 (140/1460198) while in subpopulation MID AF = 0.00764 (44/5756). AF 95% confidence interval is 0.00585. There are 3 homozygotes in GnomAdExome4. There are 78 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.732A>G	p.Pro244Pro	synonymous_variant	Exon 5 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.732A>G	p.Pro244Pro	synonymous_variant	Exon 6 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.732A>G	p.Pro244Pro	synonymous_variant	Exon 6 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.732A>G	p.Pro244Pro	synonymous_variant	Exon 6 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 link	c.732A>G	p.Pro244Pro	synonymous_variant	Exon 5 of 78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.993A>G		non_coding_transcript_exon_variant	Exon 5 of 77	2
DNAH1	ENST00000497875.1 link	n.897A>G		non_coding_transcript_exon_variant	Exon 6 of 21	2

Frequencies

GnomAD3 genomes

AF:

0.0000923

AC:

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000101

AC:

AN:

246560

AF XY:

0.000142

show subpopulations

Gnomad AFR exome

AF:

0.0000662

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000717

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000959

AC:

140

AN:

1460198

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

726322

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33430

American (AMR)

AF:

0.000202

AC:

AN:

44546

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.000337

AC:

AN:

86036

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00764

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1111080

Other (OTH)

AF:

0.000232

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000790

AC:

AN:

151852

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74188

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41370

American (AMR)

AF:

0.000131

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000417

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10552

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67918

Other (OTH)

AF:

0.000475

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000987

Hom.:

Bravo

AF:

0.0000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Oct 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

1.2

(source)

DANN

Benign

0.67

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism

(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