Genetic Variant DNAH17:c.7275+45A>G (chr17-78485915-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173628.4(DNAH17):c.7275+45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,597,128 control chromosomes in the GnomAD database, including 360,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33282 hom., cov: 31)

Exomes 𝑓: 0.67 ( 327650 hom. )

Consequence

DNAH17
NM_173628.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.104

Publications

11 publications found

Variant links:

Genes affected

DNAH17 (HGNC:2946): (dynein axonemal heavy chain 17) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. DNAH17 is a heavy chain associated with axonemal dynein (Milisav and Affara, 1998 [PubMed 9545504]).[supplied by OMIM, Mar 2008]

DNAH17 links:

DNAH17-AS1 (HGNC:48594): (DNAH17 antisense RNA 1)

DNAH17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-78485915-T-C is Benign according to our data. Variant chr17-78485915-T-C is described in ClinVar as Benign. ClinVar VariationId is 1263686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173628.4. 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
	DNAH17	NM_173628.4	MANE Select	c.7275+45A>G		intron	N/A	NP_775899.3	Q9UFH2-1
	DNAH17-AS1	NR_102401.1		n.253+753T>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DNAH17	ENST00000389840.7	TSL:5 MANE Select	c.7275+45A>G	intron	N/A	ENSP00000374490.6	Q9UFH2-1
DNAH17-AS1	ENST00000663269.1		n.273T>C	non_coding_transcript_exon	Exon 2 of 4
DNAH17	ENST00000586052.5	TSL:5	n.654+45A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.659

AC:

100002

AN:

151798

Hom.:

33256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.596

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.689

Gnomad EAS

AF:

0.637

Gnomad SAS

AF:

0.735

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.658

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.675

GnomAD2 exomes

AF:

0.692

AC:

163203

AN:

235892

AF XY:

0.692

show subpopulations

Gnomad AFR exome

AF:

0.596

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.680

Gnomad EAS exome

AF:

0.642

Gnomad FIN exome

AF:

0.667

Gnomad NFE exome

AF:

0.672

Gnomad OTH exome

AF:

0.688

GnomAD4 exome

AF:

0.672

AC:

971501

AN:

1445212

Hom.:

327650

Cov.:

AF XY:

0.674

AC XY:

483787

AN XY:

718178

show subpopulations

African (AFR)

AF:

0.594

AC:

19705

AN:

33184

American (AMR)

AF:

0.785

AC:

34111

AN:

43474

Ashkenazi Jewish (ASJ)

AF:

0.675

AC:

16952

AN:

25106

East Asian (EAS)

AF:

0.642

AC:

25414

AN:

39604

South Asian (SAS)

AF:

0.747

AC:

62984

AN:

84364

European-Finnish (FIN)

AF:

0.670

AC:

32862

AN:

49078

Middle Eastern (MID)

AF:

0.676

AC:

3807

AN:

5628

European-Non Finnish (NFE)

AF:

0.666

AC:

735733

AN:

1105012

Other (OTH)

AF:

0.668

AC:

39933

AN:

59762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

18036

36073

54109

72146

90182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19236

38472

57708

76944

96180

<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:

0.659

AC:

100081

AN:

151916

Hom.:

33282

Cov.:

AF XY:

0.662

AC XY:

49130

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.596

AC:

24690

AN:

41408

American (AMR)

AF:

0.740

AC:

11309

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

2391

AN:

3470

East Asian (EAS)

AF:

0.636

AC:

3269

AN:

5142

South Asian (SAS)

AF:

0.736

AC:

3542

AN:

4812

European-Finnish (FIN)

AF:

0.678

AC:

7142

AN:

10540

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.670

AC:

45510

AN:

67950

Other (OTH)

AF:

0.677

AC:

1426

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1722

3444

5165

6887

8609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<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:

0.634

Hom.:

6885

Bravo

AF:

0.661

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.74

(source)

DANN

Benign

0.58

PhyloP100

-0.10

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

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