NM_001206927.2:c.1549T>C

Variant summary

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

The NM_001206927.2(DNAH8):​c.1549T>C​(p.Tyr517His) variant causes a missense change. The variant allele was found at a frequency of 0.141 in 1,558,360 control chromosomes in the GnomAD database, including 17,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1386 hom., cov: 32)
Exomes 𝑓: 0.14 ( 16063 hom. )

Consequence

DNAH8
NM_001206927.2 missense

Scores

7
10

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.34

Publications

11 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: Labcorp Genetics (formerly Invitae), ClinGen
  • spermatogenic failure 5
    Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
  • primary ciliary dyskinesia
    Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

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 (MetaRNN=0.002126515).
BP6
Variant 6-38761735-T-C is Benign according to our data. Variant chr6-38761735-T-C is described in ClinVar as Benign. ClinVar VariationId is 402760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH8NM_001206927.2 linkc.1549T>C p.Tyr517His missense_variant Exon 11 of 93 ENST00000327475.11 NP_001193856.1 Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH8ENST00000327475.11 linkc.1549T>C p.Tyr517His missense_variant Exon 11 of 93 5 NM_001206927.2 ENSP00000333363.7 A0A075B6F3
DNAH8ENST00000359357.7 linkc.898T>C p.Tyr300His missense_variant Exon 9 of 91 2 ENSP00000352312.3 Q96JB1-1
DNAH8ENST00000449981.6 linkc.1549T>C p.Tyr517His missense_variant Exon 10 of 82 5 ENSP00000415331.2 H0Y7V4

Frequencies

GnomAD3 genomes
AF:
0.122
AC:
18497
AN:
152122
Hom.:
1376
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0598
Gnomad AMI
AF:
0.104
Gnomad AMR
AF:
0.215
Gnomad ASJ
AF:
0.107
Gnomad EAS
AF:
0.0154
Gnomad SAS
AF:
0.0510
Gnomad FIN
AF:
0.118
Gnomad MID
AF:
0.0949
Gnomad NFE
AF:
0.153
Gnomad OTH
AF:
0.113
GnomAD2 exomes
AF:
0.130
AC:
27051
AN:
207336
AF XY:
0.125
show subpopulations
Gnomad AFR exome
AF:
0.0568
Gnomad AMR exome
AF:
0.268
Gnomad ASJ exome
AF:
0.109
Gnomad EAS exome
AF:
0.0106
Gnomad FIN exome
AF:
0.120
Gnomad NFE exome
AF:
0.146
Gnomad OTH exome
AF:
0.130
GnomAD4 exome
AF:
0.144
AC:
201814
AN:
1406120
Hom.:
16063
Cov.:
27
AF XY:
0.140
AC XY:
98181
AN XY:
699940
show subpopulations
African (AFR)
AF:
0.0564
AC:
1676
AN:
29716
American (AMR)
AF:
0.258
AC:
8799
AN:
34078
Ashkenazi Jewish (ASJ)
AF:
0.112
AC:
2736
AN:
24506
East Asian (EAS)
AF:
0.0157
AC:
560
AN:
35766
South Asian (SAS)
AF:
0.0530
AC:
4186
AN:
78948
European-Finnish (FIN)
AF:
0.123
AC:
6447
AN:
52474
Middle Eastern (MID)
AF:
0.0925
AC:
513
AN:
5544
European-Non Finnish (NFE)
AF:
0.156
AC:
169225
AN:
1087284
Other (OTH)
AF:
0.133
AC:
7672
AN:
57804
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.466
Heterozygous variant carriers
0
7048
14096
21145
28193
35241
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
6026
12052
18078
24104
30130
<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:
0.122
AC:
18529
AN:
152240
Hom.:
1386
Cov.:
32
AF XY:
0.120
AC XY:
8929
AN XY:
74430
show subpopulations
African (AFR)
AF:
0.0598
AC:
2487
AN:
41556
American (AMR)
AF:
0.215
AC:
3288
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.107
AC:
371
AN:
3472
East Asian (EAS)
AF:
0.0154
AC:
80
AN:
5190
South Asian (SAS)
AF:
0.0506
AC:
244
AN:
4818
European-Finnish (FIN)
AF:
0.118
AC:
1252
AN:
10592
Middle Eastern (MID)
AF:
0.0952
AC:
28
AN:
294
European-Non Finnish (NFE)
AF:
0.153
AC:
10435
AN:
68008
Other (OTH)
AF:
0.118
AC:
249
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
806
1612
2418
3224
4030
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
196
392
588
784
980
<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:
0.142
Hom.:
5560
Bravo
AF:
0.127
TwinsUK
AF:
0.149
AC:
554
ALSPAC
AF:
0.162
AC:
623
ESP6500AA
AF:
0.0633
AC:
279
ESP6500EA
AF:
0.153
AC:
1313
ExAC
AF:
0.128
AC:
15513
Asia WGS
AF:
0.0770
AC:
270
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 28, 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 -

Primary ciliary dyskinesia Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Nov 10, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.072
T;T;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.86
D;D;D
MetaRNN
Benign
0.0021
T;T;T
MetaSVM
Benign
-0.87
T
MutationAssessor
Uncertain
2.1
.;.;M
PhyloP100
4.3
PrimateAI
Uncertain
0.68
T
PROVEAN
Uncertain
-3.8
.;D;D
REVEL
Benign
0.23
Sift
Benign
0.10
.;T;T
Polyphen
0.43
.;.;B
Vest4
0.30
MPC
0.44
ClinPred
0.029
T
GERP RS
6.0
Varity_R
0.49
gMVP
0.68
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: rs61748600; hg19: chr6-38729511; COSMIC: COSV59480744; COSMIC: COSV59480744; API