2-3546023-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_002936.6(RNASEH1):c.775-152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0014 in 636,342 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0038 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00065 ( 2 hom. )
Consequence
RNASEH1
NM_002936.6 intron
NM_002936.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.373
Genes affected
RNASEH1 (HGNC:18466): (ribonuclease H1) This gene encodes an endonuclease that specifically degrades the RNA of RNA-DNA hybrids and plays a key role in DNA replication and repair. Alternate in-frame start codon initiation results in the production of alternate isoforms that are directed to the mitochondria or to the nucleus. The production of the mitochondrial isoform is modulated by an upstream open reading frame (uORF). Mutations in this gene have been found in individuals with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2. Alternative splicing results in additional coding and non-coding transcript variants. Pseudogenes of this gene have been defined on chromosomes 2 and 17. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 2-3546023-C-T is Benign according to our data. Variant chr2-3546023-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1198046.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNASEH1 | NM_002936.6 | c.775-152G>A | intron_variant | ENST00000315212.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RNASEH1 | ENST00000315212.4 | c.775-152G>A | intron_variant | 1 | NM_002936.6 | P1 | |||
RNASEH1 | ENST00000436842.5 | c.*881-152G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00377 AC: 574AN: 152246Hom.: 9 Cov.: 32
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GnomAD4 exome AF: 0.000653 AC: 316AN: 483978Hom.: 2 AF XY: 0.000613 AC XY: 158AN XY: 257950
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GnomAD4 genome AF: 0.00377 AC: 574AN: 152364Hom.: 9 Cov.: 32 AF XY: 0.00356 AC XY: 265AN XY: 74504
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 28, 2019 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at