rs200850423
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_015512.5(DNAH1):c.10765G>A(p.Asp3589Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000076 in 1,605,248 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000077 ( 1 hom. )
Consequence
DNAH1
NM_015512.5 missense
NM_015512.5 missense
Scores
4
13
Clinical Significance
Conservation
PhyloP100: 5.21
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.03445351).
BP6
?
Variant 3-52394603-G-A is Benign according to our data. Variant chr3-52394603-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH1 | NM_015512.5 | c.10765G>A | p.Asp3589Asn | missense_variant | 67/78 | ENST00000420323.7 | |
DNAH1 | XM_017006129.2 | c.10834G>A | p.Asp3612Asn | missense_variant | 69/80 | ||
DNAH1 | XM_017006130.2 | c.10765G>A | p.Asp3589Asn | missense_variant | 68/79 | ||
DNAH1 | XM_017006131.2 | c.10708G>A | p.Asp3570Asn | missense_variant | 68/79 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH1 | ENST00000420323.7 | c.10765G>A | p.Asp3589Asn | missense_variant | 67/78 | 1 | NM_015512.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000351 AC: 85AN: 242370Hom.: 1 AF XY: 0.000259 AC XY: 34AN XY: 131240
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GnomAD4 exome AF: 0.0000771 AC: 112AN: 1452936Hom.: 1 Cov.: 32 AF XY: 0.0000610 AC XY: 44AN XY: 721718
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74478
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 06, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 05, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at