Genetic Variant DNAH8:c.10790+107T>G (chr6-38923292-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001206927.2(DNAH8):c.10790+107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,362,986 control chromosomes in the GnomAD database, including 17,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 5638 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12241 hom. )

Consequence

DNAH8
NM_001206927.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.224

Publications

5 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 links:

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

DNAH8-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 6-38923292-T-G is Benign according to our data. Variant chr6-38923292-T-G is described in ClinVar as [Benign]. Clinvar id is 1224224.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.10790+107T>G		intron_variant	Intron 72 of 92	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 link	c.10790+107T>G		intron_variant	Intron 72 of 92	5	NM_001206927.2	ENSP00000333363.7		A0A075B6F3

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

32930

AN:

152032

Hom.:

5624

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.116

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.123

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.0745

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.184

GnomAD4 exome

AF:

0.125

AC:

151805

AN:

1210836

Hom.:

12241

Cov.:

AF XY:

0.123

AC XY:

73725

AN XY:

601714

show subpopulations

African (AFR)

AF:

0.478

AC:

12816

AN:

26818

American (AMR)

AF:

0.130

AC:

3618

AN:

27816

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

2244

AN:

19606

East Asian (EAS)

AF:

0.275

AC:

10075

AN:

36702

South Asian (SAS)

AF:

0.0667

AC:

4389

AN:

65756

European-Finnish (FIN)

AF:

0.104

AC:

4275

AN:

41168

Middle Eastern (MID)

AF:

0.0900

AC:

374

AN:

4154

European-Non Finnish (NFE)

AF:

0.114

AC:

107068

AN:

937844

Other (OTH)

AF:

0.136

AC:

6946

AN:

50972

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5901

11801

17702

23602

29503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.217

AC:

32976

AN:

152150

Hom.:

5638

Cov.:

AF XY:

0.211

AC XY:

15694

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.471

AC:

19528

AN:

41474

American (AMR)

AF:

0.141

AC:

2155

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.123

AC:

427

AN:

3470

East Asian (EAS)

AF:

0.282

AC:

1460

AN:

5172

South Asian (SAS)

AF:

0.0735

AC:

354

AN:

4818

European-Finnish (FIN)

AF:

0.104

AC:

1105

AN:

10598

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7416

AN:

68014

Other (OTH)

AF:

0.182

AC:

385

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1125

2250

3374

4499

5624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.142

Hom.:

9918

Bravo

AF:

0.235

Asia WGS

AF:

0.183

AC:

636

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 11, 2018

GeneDx

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

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.79

PhyloP100

0.22

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

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6-38923292-T-G

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