rs80128076

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.5853G>A(p.Val1951Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,614,008 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 30 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.154

Publications

3 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=-0.56).

BP6

Variant 3-52368828-G-A is Benign according to our data. Variant chr3-52368828-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.154 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00333 (507/152308) while in subpopulation SAS AF = 0.00643 (31/4824). AF 95% confidence interval is 0.00465. There are 2 homozygotes in GnomAd4. There are 252 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.5853G>A	p.Val1951Val	synonymous_variant	Exon 37 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.5922G>A	p.Val1974Val	synonymous_variant	Exon 39 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.5853G>A	p.Val1951Val	synonymous_variant	Exon 38 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.5922G>A	p.Val1974Val	synonymous_variant	Exon 39 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 link	c.5853G>A	p.Val1951Val	synonymous_variant	Exon 37 of 78	1	NM_015512.5	ENSP00000401514.2		Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.6114G>A		non_coding_transcript_exon_variant	Exon 37 of 77	2

Frequencies

GnomAD3 genomes

AF:

0.00333

AC:

507

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000844

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00386

AC:

963

AN:

249268

AF XY:

0.00419

show subpopulations

Gnomad AFR exome

AF:

0.000710

Gnomad AMR exome

AF:

0.00293

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00443

Gnomad OTH exome

AF:

0.00528

GnomAD4 exome

AF:

0.00442

AC:

6456

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

3309

AN XY:

727132

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

33480

American (AMR)

AF:

0.00250

AC:

112

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00494

AC:

129

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00793

AC:

684

AN:

86258

European-Finnish (FIN)

AF:

0.00182

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00590

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00458

AC:

5092

AN:

1111868

Other (OTH)

AF:

0.00462

AC:

279

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

388

776

1163

1551

1939

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.00333

AC:

507

AN:

152308

Hom.:

Cov.:

AF XY:

0.00338

AC XY:

252

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41570

American (AMR)

AF:

0.00464

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00643

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000848

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00478

AC:

325

AN:

68032

Other (OTH)

AF:

0.00426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

109

136

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:

0.00390

Hom.:

Bravo

AF:

0.00297

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.00513

EpiControl

AF:

0.00462

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

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

DNAH1: BP4, BP7, BS2 -

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

-0.56

CADD

Benign

7.1

(source)

DANN

Benign

0.78

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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