chr12-124325482-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_006312.6(NCOR2):c.7465G>A(p.Ala2489Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,336,114 control chromosomes in the GnomAD database, including 728 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.018 ( 91 hom., cov: 30)
Exomes 𝑓: 0.013 ( 637 hom. )
Consequence
NCOR2
NM_006312.6 missense
NM_006312.6 missense
Scores
2
14
Clinical Significance
Conservation
PhyloP100: 0.159
Genes affected
NCOR2 (HGNC:7673): (nuclear receptor corepressor 2) This gene encodes a nuclear receptor co-repressor that mediates transcriptional silencing of certain target genes. The encoded protein is a member of a family of thyroid hormone- and retinoic acid receptor-associated co-repressors. This protein acts as part of a multisubunit complex which includes histone deacetylases to modify chromatin structure that prevents basal transcriptional activity of target genes. Aberrant expression of this gene is associated with certain cancers. Alternate splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Apr 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0015721619).
BP6
?
Variant 12-124325482-C-T is Benign according to our data. Variant chr12-124325482-C-T is described in ClinVar as [Benign]. Clinvar id is 1271601.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCOR2 | NM_006312.6 | c.7465G>A | p.Ala2489Thr | missense_variant | 49/49 | ENST00000405201.6 | |
NCOR2 | NM_001206654.2 | c.7435G>A | p.Ala2479Thr | missense_variant | 48/48 | ||
NCOR2 | NM_001077261.4 | c.7297G>A | p.Ala2433Thr | missense_variant | 48/48 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCOR2 | ENST00000405201.6 | c.7465G>A | p.Ala2489Thr | missense_variant | 49/49 | 1 | NM_006312.6 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.0178 AC: 2611AN: 146388Hom.: 90 Cov.: 30
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GnomAD3 exomes AF: 0.0536 AC: 1537AN: 28692Hom.: 92 AF XY: 0.0562 AC XY: 836AN XY: 14866
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GnomAD4 exome AF: 0.0129 AC: 15364AN: 1189626Hom.: 637 Cov.: 38 AF XY: 0.0150 AC XY: 8666AN XY: 578526
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GnomAD4 genome ? AF: 0.0179 AC: 2620AN: 146488Hom.: 91 Cov.: 30 AF XY: 0.0241 AC XY: 1709AN XY: 71006
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 17, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.;.;N
REVEL
Benign
Sift
Benign
T;T;.;.;T
Sift4G
Benign
T;T;T;T;T
Vest4
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at