rs541631905
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_001369.3(DNAH5):c.7620G>A(p.Thr2540Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,050 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 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000017 ( 0 hom. )
Consequence
DNAH5
NM_001369.3 synonymous
NM_001369.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.418
Genes affected
DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP6
Variant 5-13809176-C-T is Benign according to our data. Variant chr5-13809176-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 525473.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.418 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.7620G>A | p.Thr2540Thr | synonymous_variant | 46/79 | ENST00000265104.5 | NP_001360.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.7620G>A | p.Thr2540Thr | synonymous_variant | 46/79 | 1 | NM_001369.3 | ENSP00000265104.4 | ||
DNAH5 | ENST00000681290.1 | c.7575G>A | p.Thr2525Thr | synonymous_variant | 46/79 | ENSP00000505288.1 | ||||
DNAH5 | ENST00000512443.1 | n.476G>A | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251470Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135912
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GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461812Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727200
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GnomAD4 genome AF: 0.0000525 AC: 8AN: 152238Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74434
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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 submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at