dbSNP rs200564814: DNAH8:p.Thr1504Thr (chr6-38842413-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001206927.2(DNAH8):c.4512C>T(p.Thr1504Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,611,372 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 1 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.870

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: 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 -13 ACMG points.

BP4

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

BP6

Variant 6-38842413-C-T is Benign according to our data. Variant chr6-38842413-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 454572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.87 with no splicing effect.

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.4512C>T	p.Thr1504Thr	synonymous	Exon 34 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.3861C>T	p.Thr1287Thr	synonymous	Exon 33 of 92	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.4512C>T	p.Thr1504Thr	synonymous	Exon 34 of 93	ENSP00000333363.7	A0A075B6F3
DNAH8	ENST00000359357.7	TSL:2	c.3861C>T	p.Thr1287Thr	synonymous	Exon 32 of 91	ENSP00000352312.3	Q96JB1-1
DNAH8	ENST00000449981.6	TSL:5	c.4512C>T	p.Thr1504Thr	synonymous	Exon 33 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000372

AC:

AN:

250034

AF XY:

0.000400

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00319

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000292

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000568

AC:

829

AN:

1459444

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

401

AN XY:

725912

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33420

American (AMR)

AF:

0.000202

AC:

AN:

44488

Ashkenazi Jewish (ASJ)

AF:

0.00330

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39586

South Asian (SAS)

AF:

0.000408

AC:

AN:

85690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000593

AC:

659

AN:

1110768

Other (OTH)

AF:

0.000581

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

115

154

192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

150

<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:

0.000316

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41340

American (AMR)

AF:

0.000786

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000415

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

67996

Other (OTH)

AF:

0.000959

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.000491

Hom.:

Bravo

AF:

0.000325

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

DNAH8-related disorder (1)

not provided (1)

Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.5

(source)

DANN

Benign

0.58

PhyloP100

-0.87

Mutation Taster

=99/1

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

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