dbSNP rs149534667: DNAH8:p.Gln628Gln (chr6-38775873-A-G) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001206927.2(DNAH8):c.1884A>G(p.Gln628Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 1,612,684 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 2 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.704

Publications

0 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: Labcorp Genetics (formerly Invitae), ClinGen
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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 6-38775873-A-G is Benign according to our data. Variant chr6-38775873-A-G is described in ClinVar as Benign. ClinVar VariationId is 454559.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.704 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00289 (440/152356) while in subpopulation AFR AF = 0.00984 (409/41586). AF 95% confidence interval is 0.00905. There are 2 homozygotes in GnomAd4. There are 210 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.1884A>G	p.Gln628Gln	synonymous_variant	Exon 13 of 93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH8	ENST00000327475.11 link	c.1884A>G	p.Gln628Gln	synonymous_variant	Exon 13 of 93	5	NM_001206927.2	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7 link	c.1233A>G	p.Gln411Gln	synonymous_variant	Exon 11 of 91	2		ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6 link	c.1884A>G	p.Gln628Gln	synonymous_variant	Exon 12 of 82	5		ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00986

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.000761

AC:

191

AN:

250838

AF XY:

0.000685

show subpopulations

Gnomad AFR exome

AF:

0.00955

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000327

AC:

477

AN:

1460328

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

239

AN XY:

726622

show subpopulations

African (AFR)

AF:

0.00981

AC:

328

AN:

33430

American (AMR)

AF:

0.000626

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39562

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000702

AC:

AN:

1110818

Other (OTH)

AF:

0.000663

AC:

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152356

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00984

AC:

409

AN:

41586

American (AMR)

AF:

0.00124

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00167

Hom.:

Bravo

AF:

0.00351

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Dec 26, 2024

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

-0.59

CADD

Benign

0.47

(source)

DANN

Benign

0.40

PhyloP100

-0.70

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

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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