chr2-17759914-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_001130009.3(GEN1):c.-15-15T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,608,706 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00035 ( 1 hom. )
Consequence
GEN1
NM_001130009.3 splice_polypyrimidine_tract, intron
NM_001130009.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.692
Genes affected
GEN1 (HGNC:26881): (GEN1 Holliday junction 5' flap endonuclease) This gene encodes a member of the Rad2/xeroderma pigmentosum group G nuclease family, whose members are characterized by N-terminal and internal xeroderma pigmentosum group G nuclease domains followed by helix-hairpin-helix domains and disordered C-terminal domains. The protein encoded by this gene is involved in resolution of Holliday junctions, which are intermediate four-way structures that covalently link DNA during homologous recombination and double-strand break repair. The protein resolves Holliday junctions by creating dual incisions across the junction to produce nicked duplex products that can be ligated. In addition, this protein has been found to localize to centrosomes where it has been implicated in regulation of centrosome integrity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]
SMC6 (HGNC:20466): (structural maintenance of chromosomes 6) Enables ubiquitin protein ligase binding activity. Involved in several processes, including cellular senescence; positive regulation of chromosome segregation; and telomere maintenance via recombination. Located in chromosome and nuclear body. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 2-17759914-T-G is Benign according to our data. Variant chr2-17759914-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 223816.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GEN1 | NM_001130009.3 | c.-15-15T>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000381254.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GEN1 | ENST00000381254.7 | c.-15-15T>G | splice_polypyrimidine_tract_variant, intron_variant | 5 | NM_001130009.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000348 AC: 53AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000607 AC: 151AN: 248720Hom.: 0 AF XY: 0.000714 AC XY: 96AN XY: 134406
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GnomAD4 exome AF: 0.000345 AC: 503AN: 1456364Hom.: 1 Cov.: 30 AF XY: 0.000402 AC XY: 291AN XY: 724464
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, no assertion criteria provided | clinical testing | University of Washington Department of Laboratory Medicine, University of Washington | Dec 01, 2015 | - - |
Computational scores
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Benign
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Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 15
Find out detailed SpliceAI scores and Pangolin per-transcript scores at