X-55006997-A-G
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2
The NM_014481.4(APEX2):āc.1119A>Gā(p.Gln373=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000826 in 1,210,232 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000018 ( 0 hom., 0 hem., cov: 24)
Exomes š: 0.0000073 ( 0 hom. 2 hem. )
Consequence
APEX2
NM_014481.4 synonymous
NM_014481.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.52
Genes affected
APEX2 (HGNC:17889): (apurinic/apyrimidinic endodeoxyribonuclease 2) Apurinic/apyrimidinic (AP) sites occur frequently in DNA molecules by spontaneous hydrolysis, by DNA damaging agents or by DNA glycosylases that remove specific abnormal bases. AP sites are pre-mutagenic lesions that can prevent normal DNA replication so the cell contains systems to identify and repair such sites. Class II AP endonucleases cleave the phosphodiester backbone 5' to the AP site. This gene encodes a protein shown to have a weak class II AP endonuclease activity. Most of the encoded protein is located in the nucleus but some is also present in mitochondria. This protein may play an important role in both nuclear and mitochondrial base excision repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant X-55006997-A-G is Benign according to our data. Variant chrX-55006997-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 681052.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.52 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APEX2 | NM_014481.4 | c.1119A>G | p.Gln373= | synonymous_variant | 6/6 | ENST00000374987.4 | |
APEX2 | NM_001271748.2 | c.606A>G | p.Gln202= | synonymous_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APEX2 | ENST00000374987.4 | c.1119A>G | p.Gln373= | synonymous_variant | 6/6 | 1 | NM_014481.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000178 AC: 2AN: 112094Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34260
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GnomAD3 exomes AF: 0.00000547 AC: 1AN: 182955Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67423
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GnomAD4 exome AF: 0.00000729 AC: 8AN: 1098138Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2AN XY: 363492
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GnomAD4 genome AF: 0.0000178 AC: 2AN: 112094Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34260
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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 | Apr 04, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
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