dbSNP rs3737094: DNAH8:p.Leu4373Leu (chr6-38990077-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001206927.2(DNAH8):c.13119A>G(p.Leu4373Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,592,200 control chromosomes in the GnomAD database, including 149,080 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.40 ( 12565 hom., cov: 32)

Exomes 𝑓: 0.43 ( 136515 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.316

Publications

15 publications found

Variant links:

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8 Gene-Disease associations (from GenCC):

spermatogenic failure 46
Inheritance: AR Classification: STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)
spermatogenic failure 5
Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
primary ciliary dyskinesia
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

DNAH8 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=-0.91).

BP6

Variant 6-38990077-A-G is Benign according to our data. Variant chr6-38990077-A-G is described in ClinVar as Benign. ClinVar VariationId is 257629.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.316 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.13119A>G	p.Leu4373Leu	synonymous	Exon 88 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.12468A>G	p.Leu4156Leu	synonymous	Exon 87 of 92	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.13119A>G	p.Leu4373Leu	synonymous	Exon 88 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.12468A>G	p.Leu4156Leu	synonymous	Exon 86 of 91	ENSP00000352312.3	Q96JB1-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

60734

AN:

151854

Hom.:

12554

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.466

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.295

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.399

GnomAD2 exomes

AF:

0.392

AC:

98333

AN:

250694

AF XY:

0.393

show subpopulations

Gnomad AFR exome

AF:

0.326

Gnomad AMR exome

AF:

0.334

Gnomad ASJ exome

AF:

0.400

Gnomad EAS exome

AF:

0.255

Gnomad FIN exome

AF:

0.439

Gnomad NFE exome

AF:

0.454

Gnomad OTH exome

AF:

0.424

GnomAD4 exome

AF:

0.430

AC:

619660

AN:

1440228

Hom.:

136515

Cov.:

AF XY:

0.428

AC XY:

307097

AN XY:

717998

show subpopulations

African (AFR)

AF:

0.324

AC:

10726

AN:

33056

American (AMR)

AF:

0.343

AC:

15276

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.397

AC:

10316

AN:

25986

East Asian (EAS)

AF:

0.240

AC:

9502

AN:

39572

South Asian (SAS)

AF:

0.302

AC:

25893

AN:

85740

European-Finnish (FIN)

AF:

0.446

AC:

23795

AN:

53384

Middle Eastern (MID)

AF:

0.444

AC:

2546

AN:

5732

European-Non Finnish (NFE)

AF:

0.454

AC:

496297

AN:

1092524

Other (OTH)

AF:

0.424

AC:

25309

AN:

59654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

15280

30560

45839

61119

76399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14528

29056

43584

58112

72640

<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:

0.400

AC:

60779

AN:

151972

Hom.:

12565

Cov.:

AF XY:

0.397

AC XY:

29470

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.336

AC:

13925

AN:

41434

American (AMR)

AF:

0.380

AC:

5808

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1352

AN:

3470

East Asian (EAS)

AF:

0.255

AC:

1317

AN:

5174

South Asian (SAS)

AF:

0.296

AC:

1425

AN:

4810

European-Finnish (FIN)

AF:

0.446

AC:

4707

AN:

10550

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.454

AC:

30856

AN:

67938

Other (OTH)

AF:

0.399

AC:

842

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1844

3689

5533

7378

9222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

574

1148

1722

2296

2870

<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:

0.428

Hom.:

12828

Bravo

AF:

0.392

Asia WGS

AF:

0.298

AC:

1037

AN:

3478

EpiCase

AF:

0.458

EpiControl

AF:

0.455

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.48

(source)

DANN

Benign

0.54

PhyloP100

-0.32

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over