rs77639782

Variant names:

Variant summary

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

The ENST00000420323.7(DNAH1):c.3111G>A(p.Ser1037Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00761 in 1,613,952 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 67 hom. )

Consequence

DNAH1
ENST00000420323.7 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.74

Publications

1 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=-0.71).

BP6

Variant 3-52353186-G-A is Benign according to our data. Variant chr3-52353186-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 478438.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.74 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00416 (634/152318) while in subpopulation NFE AF = 0.00728 (495/68028). AF 95% confidence interval is 0.00675. There are 0 homozygotes in GnomAd4. There are 278 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 67 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000420323.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH1	NM_015512.5	MANE Select	c.3111G>A	p.Ser1037Ser	synonymous	Exon 19 of 78	NP_056327.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DNAH1	ENST00000420323.7	TSL:1 MANE Select	c.3111G>A	p.Ser1037Ser	synonymous	Exon 19 of 78	ENSP00000401514.2
DNAH1	ENST00000486752.5	TSL:2	n.3372G>A		non_coding_transcript_exon	Exon 19 of 77
DNAH1	ENST00000497875.1	TSL:2	n.3276G>A		non_coding_transcript_exon	Exon 20 of 21

Frequencies

GnomAD3 genomes

AF:

0.00417

AC:

635

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00254

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00728

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00457

AC:

1139

AN:

249108

AF XY:

0.00464

show subpopulations

Gnomad AFR exome

AF:

0.00155

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00204

Gnomad NFE exome

AF:

0.00789

Gnomad OTH exome

AF:

0.00364

GnomAD4 exome

AF:

0.00797

AC:

11656

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00787

AC XY:

5722

AN XY:

727106

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

33480

American (AMR)

AF:

0.00190

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000765

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00332

AC:

286

AN:

86254

European-Finnish (FIN)

AF:

0.00244

AC:

130

AN:

53354

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00963

AC:

10706

AN:

1111850

Other (OTH)

AF:

0.00666

AC:

402

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

643

1287

1930

2574

3217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

428

856

1284

1712

2140

<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:

0.00416

AC:

634

AN:

152318

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

278

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41570

American (AMR)

AF:

0.00229

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00290

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00254

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00728

AC:

495

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

101

134

168

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:

0.00523

Hom.:

Bravo

AF:

0.00414

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00692

EpiControl

AF:

0.00771

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.19

(source)

DANN

Benign

0.80

PhyloP100

-3.7

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over