rs180859001

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_001206927.2(DNAH8):c.9839A>T(p.Gln3280Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000048 in 1,603,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. Q3280Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.92

Publications

3 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: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0150668025).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00021 (32/152354) while in subpopulation AMR AF = 0.00196 (30/15302). AF 95% confidence interval is 0.00141. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH8	NM_001206927.2	MANE Select	c.9839A>T	p.Gln3280Leu	missense	Exon 66 of 93	NP_001193856.1	A0A075B6F3
DNAH8	NM_001371.4		c.9188A>T	p.Gln3063Leu	missense	Exon 65 of 92	NP_001362.2	Q96JB1-1
DNAH8-AS1	NR_038401.1		n.783-3729T>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.9839A>T	p.Gln3280Leu	missense	Exon 66 of 93	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7	TSL:2	c.9188A>T	p.Gln3063Leu	missense	Exon 64 of 91	ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6	TSL:5	c.9839A>T	p.Gln3280Leu	missense	Exon 65 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000917

AC:

AN:

250782

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000668

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000310

AC:

AN:

1450700

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

722548

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33232

American (AMR)

AF:

0.000895

AC:

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26058

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.00

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101894

Other (OTH)

AF:

0.0000833

AC:

AN:

60046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.000210

AC:

AN:

152354

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74512

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41586

American (AMR)

AF:

0.00196

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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:

0.0000564

Hom.:

Bravo

AF:

0.000257

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.034

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.78

M_CAP

Benign

0.0064

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.87

PhyloP100

3.9

PrimateAI

Uncertain

0.49

PROVEAN

Benign

3.2

REVEL

Benign

0.19

Sift

Benign

1.0

Polyphen

0.0

Vest4

0.46

MVP

0.68

MPC

0.12

ClinPred

0.099

GERP RS

5.8

Varity_R

0.15

gMVP

0.53

Mutation Taster

=64/36

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

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