chr17-78475284-G-A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_173628.4(DNAH17):​c.8505C>T​(p.Asp2835Asp) variant causes a synonymous change. The variant allele was found at a frequency of 0.123 in 1,613,812 control chromosomes in the GnomAD database, including 13,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1129 hom., cov: 32)
Exomes 𝑓: 0.12 ( 11963 hom. )

Consequence

DNAH17
NM_173628.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 4.10

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 Gene-Disease associations (from GenCC):
  • spermatogenic failure 39
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
  • non-syndromic male infertility due to sperm motility disorder
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 17-78475284-G-A is Benign according to our data. Variant chr17-78475284-G-A is described in CliVar as Benign. Clinvar id is 402678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-78475284-G-A is described in CliVar as Benign. Clinvar id is 402678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH17NM_173628.4 linkc.8505C>T p.Asp2835Asp synonymous_variant Exon 54 of 81 ENST00000389840.7 NP_775899.3 Q9UFH2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH17ENST00000389840.7 linkc.8505C>T p.Asp2835Asp synonymous_variant Exon 54 of 81 5 NM_173628.4 ENSP00000374490.6 Q9UFH2-1
DNAH17ENST00000586052.5 linkn.1887C>T non_coding_transcript_exon_variant Exon 10 of 35 5

Frequencies

GnomAD3 genomes
AF:
0.116
AC:
17638
AN:
152132
Hom.:
1123
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0867
Gnomad AMI
AF:
0.138
Gnomad AMR
AF:
0.0993
Gnomad ASJ
AF:
0.115
Gnomad EAS
AF:
0.190
Gnomad SAS
AF:
0.180
Gnomad FIN
AF:
0.161
Gnomad MID
AF:
0.114
Gnomad NFE
AF:
0.120
Gnomad OTH
AF:
0.119
GnomAD2 exomes
AF:
0.130
AC:
32432
AN:
248784
AF XY:
0.136
show subpopulations
Gnomad AFR exome
AF:
0.0835
Gnomad AMR exome
AF:
0.0749
Gnomad ASJ exome
AF:
0.106
Gnomad EAS exome
AF:
0.195
Gnomad FIN exome
AF:
0.159
Gnomad NFE exome
AF:
0.125
Gnomad OTH exome
AF:
0.135
GnomAD4 exome
AF:
0.124
AC:
181214
AN:
1461562
Hom.:
11963
Cov.:
33
AF XY:
0.126
AC XY:
91705
AN XY:
727062
show subpopulations
African (AFR)
AF:
0.0821
AC:
2750
AN:
33480
American (AMR)
AF:
0.0772
AC:
3454
AN:
44712
Ashkenazi Jewish (ASJ)
AF:
0.109
AC:
2854
AN:
26136
East Asian (EAS)
AF:
0.157
AC:
6221
AN:
39698
South Asian (SAS)
AF:
0.186
AC:
16029
AN:
86248
European-Finnish (FIN)
AF:
0.159
AC:
8509
AN:
53378
Middle Eastern (MID)
AF:
0.125
AC:
720
AN:
5768
European-Non Finnish (NFE)
AF:
0.120
AC:
132914
AN:
1111774
Other (OTH)
AF:
0.129
AC:
7763
AN:
60368
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
8715
17431
26146
34862
43577
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
4848
9696
14544
19392
24240
<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:
0.116
AC:
17660
AN:
152250
Hom.:
1129
Cov.:
32
AF XY:
0.119
AC XY:
8844
AN XY:
74456
show subpopulations
African (AFR)
AF:
0.0871
AC:
3619
AN:
41550
American (AMR)
AF:
0.0990
AC:
1514
AN:
15300
Ashkenazi Jewish (ASJ)
AF:
0.115
AC:
399
AN:
3472
East Asian (EAS)
AF:
0.190
AC:
981
AN:
5172
South Asian (SAS)
AF:
0.180
AC:
869
AN:
4824
European-Finnish (FIN)
AF:
0.161
AC:
1709
AN:
10598
Middle Eastern (MID)
AF:
0.112
AC:
33
AN:
294
European-Non Finnish (NFE)
AF:
0.120
AC:
8151
AN:
68014
Other (OTH)
AF:
0.122
AC:
259
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
795
1591
2386
3182
3977
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
208
416
624
832
1040
<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:
0.118
Hom.:
709
Bravo
AF:
0.108
Asia WGS
AF:
0.201
AC:
700
AN:
3478
EpiCase
AF:
0.124
EpiControl
AF:
0.128

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
May 04, 2021
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

not specified Benign:1
Mar 29, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DNAH17-related disorder Benign:1
Oct 28, 2019
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
CADD
Benign
8.6
DANN
Benign
0.91
PhyloP100
4.1
Mutation Taster
=93/7
polymorphism (auto)

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

Other links and lift over

dbSNP: rs61746438; hg19: chr17-76471366; COSMIC: COSV67754468; COSMIC: COSV67754468; API