Genetic Variant DNAH8:p.Asp3860Asp (chr6-38937990-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS1

The NM_001206927.2(DNAH8):c.11580C>T(p.Asp3860Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,613,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.43

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 links:

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

DNAH8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 6-38937990-C-T is Benign according to our data. Variant chr6-38937990-C-T is described in ClinVar as Benign. ClinVar VariationId is 238632.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.42 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00146 (222/151684) while in subpopulation AFR AF = 0.00506 (209/41290). AF 95% confidence interval is 0.0045. There are 0 homozygotes in GnomAd4. There are 100 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2 link	c.11580C>T	p.Asp3860Asp	synonymous_variant	Exon 78 of 93	ENST00000327475.11	NP_001193856.1	Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 link	c.11580C>T	p.Asp3860Asp	synonymous_variant	Exon 78 of 93	5	NM_001206927.2	ENSP00000333363.7		A0A075B6F3

Frequencies

GnomAD3 genomes

AF:

0.00148

AC:

224

AN:

151570

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00513

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000725

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000390

AC:

AN:

251116

AF XY:

0.000258

show subpopulations

Gnomad AFR exome

AF:

0.00461

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000219

AC:

320

AN:

1461780

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

157

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.00544

AC:

182

AN:

33476

American (AMR)

AF:

0.000201

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.000429

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00434

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000342

AC:

AN:

1111926

Other (OTH)

AF:

0.000480

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.00146

AC:

222

AN:

151684

Hom.:

Cov.:

AF XY:

0.00135

AC XY:

100

AN XY:

74104

show subpopulations

African (AFR)

AF:

0.00506

AC:

209

AN:

41290

American (AMR)

AF:

0.000724

AC:

AN:

15192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.000208

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10488

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

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:

0.000780

Hom.:

Bravo

AF:

0.00168

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Jan 06, 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

-0.38

CADD

Benign

0.046

(source)

DANN

Benign

0.82

PhyloP100

-1.4

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