3-52371978-T-G
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_015512.5(DNAH1):c.6558T>G(p.Ala2186=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000281 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00027 ( 0 hom. )
Consequence
DNAH1
NM_015512.5 synonymous
NM_015512.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.111
Genes affected
DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 3-52371978-T-G is Benign according to our data. Variant chr3-52371978-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 478480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.111 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.6558T>G | p.Ala2186= | synonymous_variant | 42/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.6627T>G | p.Ala2209= | synonymous_variant | 44/80 | ||
DNAH1 | XM_017006130.2 | c.6558T>G | p.Ala2186= | synonymous_variant | 43/79 | ||
DNAH1 | XM_017006131.2 | c.6627T>G | p.Ala2209= | synonymous_variant | 44/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.6558T>G | p.Ala2186= | synonymous_variant | 42/78 | 1 | NM_015512.5 | P1 | |
DNAH1 | ENST00000486752.5 | n.6819T>G | non_coding_transcript_exon_variant | 42/77 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000362 AC: 55AN: 152088Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
55
AN:
152088
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000313 AC: 78AN: 249056Hom.: 1 AF XY: 0.000259 AC XY: 35AN XY: 135124
GnomAD3 exomes
AF:
AC:
78
AN:
249056
Hom.:
AF XY:
AC XY:
35
AN XY:
135124
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000272 AC: 398AN: 1461528Hom.: 0 Cov.: 32 AF XY: 0.000275 AC XY: 200AN XY: 727034
GnomAD4 exome
AF:
AC:
398
AN:
1461528
Hom.:
Cov.:
32
AF XY:
AC XY:
200
AN XY:
727034
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000361 AC: 55AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.000349 AC XY: 26AN XY: 74414
GnomAD4 genome
?
AF:
AC:
55
AN:
152206
Hom.:
Cov.:
33
AF XY:
AC XY:
26
AN XY:
74414
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 20, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | DNAH1: BP4, BP7 - |
DNAH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 28, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at