rs61748602

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001206927.2(DNAH8):​c.4084-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00624 in 1,575,248 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 2 hom., cov: 31)
Exomes 𝑓: 0.0063 ( 49 hom. )

Consequence

DNAH8
NM_001206927.2 splice_region, intron

Scores

2
Splicing: ADA: 0.0002234
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.436

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: 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 (BayesDel_noAF=-0.82).
BP6
Variant 6-38828180-G-T is Benign according to our data. Variant chr6-38828180-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38828180-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38828180-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38828180-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38828180-G-T is described in CliVar as Benign/Likely_benign. Clinvar id is 238645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00526 (801/152190) while in subpopulation NFE AF = 0.00697 (474/67972). AF 95% confidence interval is 0.00645. There are 2 homozygotes in GnomAd4. There are 403 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH8NM_001206927.2 linkc.4084-4G>T splice_region_variant, intron_variant Intron 29 of 92 ENST00000327475.11 NP_001193856.1 Q96JB1Q8IU65A0A075B6F3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH8ENST00000327475.11 linkc.4084-4G>T splice_region_variant, intron_variant Intron 29 of 92 5 NM_001206927.2 ENSP00000333363.7 A0A075B6F3
DNAH8ENST00000359357.7 linkc.3433-4G>T splice_region_variant, intron_variant Intron 27 of 90 2 ENSP00000352312.3 Q96JB1-1
DNAH8ENST00000449981.6 linkc.4084-4G>T splice_region_variant, intron_variant Intron 28 of 81 5 ENSP00000415331.2 H0Y7V4

Frequencies

GnomAD3 genomes
AF:
0.00527
AC:
801
AN:
152072
Hom.:
2
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00426
Gnomad ASJ
AF:
0.0210
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.0123
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00697
Gnomad OTH
AF:
0.00479
GnomAD2 exomes
AF:
0.00611
AC:
1403
AN:
229690
AF XY:
0.00621
show subpopulations
Gnomad AFR exome
AF:
0.000791
Gnomad AMR exome
AF:
0.00314
Gnomad ASJ exome
AF:
0.0196
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0144
Gnomad NFE exome
AF:
0.00665
Gnomad OTH exome
AF:
0.00797
GnomAD4 exome
AF:
0.00634
AC:
9026
AN:
1423058
Hom.:
49
Cov.:
27
AF XY:
0.00634
AC XY:
4485
AN XY:
707444
show subpopulations
African (AFR)
AF:
0.000345
AC:
11
AN:
31918
American (AMR)
AF:
0.00330
AC:
130
AN:
39382
Ashkenazi Jewish (ASJ)
AF:
0.0180
AC:
461
AN:
25668
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38476
South Asian (SAS)
AF:
0.00189
AC:
148
AN:
78414
European-Finnish (FIN)
AF:
0.0155
AC:
822
AN:
53098
Middle Eastern (MID)
AF:
0.00122
AC:
7
AN:
5722
European-Non Finnish (NFE)
AF:
0.00642
AC:
7002
AN:
1091266
Other (OTH)
AF:
0.00753
AC:
445
AN:
59114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.472
Heterozygous variant carriers
0
370
740
1109
1479
1849
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
252
504
756
1008
1260
<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:
0.00526
AC:
801
AN:
152190
Hom.:
2
Cov.:
31
AF XY:
0.00542
AC XY:
403
AN XY:
74394
show subpopulations
African (AFR)
AF:
0.00101
AC:
42
AN:
41548
American (AMR)
AF:
0.00425
AC:
65
AN:
15284
Ashkenazi Jewish (ASJ)
AF:
0.0210
AC:
73
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.00145
AC:
7
AN:
4824
European-Finnish (FIN)
AF:
0.0123
AC:
130
AN:
10596
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00697
AC:
474
AN:
67972
Other (OTH)
AF:
0.00474
AC:
10
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
45
91
136
182
227
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00656
Hom.:
3
Bravo
AF:
0.00478
Asia WGS
AF:
0.000289
AC:
1
AN:
3474

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Jan 28, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Oct 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

DNAH8: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
7.2
DANN
Benign
0.47
PhyloP100
-0.44
Mutation Taster
=99/1
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00022
dbscSNV1_RF
Benign
0.0080
SpliceAI score (max)
0.34
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.34
Position offset: 27

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs61748602; hg19: chr6-38795956; API