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GeneBe

rs45600141

chr6-39026553-C-Gchr6-39026553-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_001206927.2(DNAH8):c.13722C>G(p.Leu4574=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 1,608,372 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 (★). Synonymous variant affecting the same amino acid position (i.e. L4574L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00080 ( 1 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.515
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 6-39026553-C-G is Benign according to our data. Variant chr6-39026553-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 414425.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.515 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000802 (1168/1456102) while in subpopulation NFE AF= 0.000939 (1042/1110126). AF 95% confidence interval is 0.000891. There are 1 homozygotes in gnomad4_exome. There are 587 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAH8NM_001206927.2 linkuse as main transcriptc.13722C>G p.Leu4574= synonymous_variant 92/93 ENST00000327475.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAH8ENST00000327475.11 linkuse as main transcriptc.13722C>G p.Leu4574= synonymous_variant 92/935 NM_001206927.2 P2
DNAH8ENST00000359357.7 linkuse as main transcriptc.13071C>G p.Leu4357= synonymous_variant 90/912 A2Q96JB1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000493
AC:
75
AN:
152152
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000867
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000716
AC:
176
AN:
245956
Hom.:
0
AF XY:
0.000744
AC XY:
99
AN XY:
133124
show subpopulations
Gnomad AFR exome
AF:
0.0000620
Gnomad AMR exome
AF:
0.000211
Gnomad ASJ exome
AF:
0.000512
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000564
Gnomad FIN exome
AF:
0.0000488
Gnomad NFE exome
AF:
0.00125
Gnomad OTH exome
AF:
0.000836
GnomAD4 exome
AF:
0.000802
AC:
1168
AN:
1456102
Hom.:
1
Cov.:
31
AF XY:
0.000811
AC XY:
587
AN XY:
724186
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
Gnomad4 AMR exome
AF:
0.000277
Gnomad4 ASJ exome
AF:
0.000271
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000536
Gnomad4 FIN exome
AF:
0.000191
Gnomad4 NFE exome
AF:
0.000939
Gnomad4 OTH exome
AF:
0.000798
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000493
AC:
75
AN:
152270
Hom.:
0
Cov.:
33
AF XY:
0.000510
AC XY:
38
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000867
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000341
Hom.:
0
Bravo
AF:
0.000525
EpiCase
AF:
0.00115
EpiControl
AF:
0.00160

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
4.8
Dann
Benign
0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs45600141; hg19: chr6-38994329; API