rs1348689
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001369.3(DNAH5):c.6264C>T(p.Ala2088=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,612,658 control chromosomes in the GnomAD database, including 114,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A2088A) has been classified as Likely benign.
Frequency
Consequence
NM_001369.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAH5 | NM_001369.3 | c.6264C>T | p.Ala2088= | synonymous_variant | 38/79 | ENST00000265104.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAH5 | ENST00000265104.5 | c.6264C>T | p.Ala2088= | synonymous_variant | 38/79 | 1 | NM_001369.3 | P4 | |
DNAH5 | ENST00000681290.1 | c.6219C>T | p.Ala2073= | synonymous_variant | 38/79 | A1 | |||
DNAH5 | ENST00000683090.1 | n.1195C>T | non_coding_transcript_exon_variant | 3/7 |
Frequencies
GnomAD3 genomes ? AF: 0.398 AC: 60495AN: 151858Hom.: 12267 Cov.: 33
GnomAD3 exomes AF: 0.385 AC: 96523AN: 250998Hom.: 19222 AF XY: 0.379 AC XY: 51433AN XY: 135666
GnomAD4 exome AF: 0.371 AC: 541740AN: 1460680Hom.: 101984 Cov.: 37 AF XY: 0.369 AC XY: 267886AN XY: 726712
GnomAD4 genome ? AF: 0.398 AC: 60548AN: 151978Hom.: 12283 Cov.: 33 AF XY: 0.396 AC XY: 29383AN XY: 74278
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 21, 2013 | Ala2088Ala in exon 38 of DNAH5: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 45.6% (2011/4406) of African American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs1348689). - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Primary ciliary dyskinesia Benign:3
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 10, 2014 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Primary ciliary dyskinesia 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Pars Genome Lab | Jun 15, 2021 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at