rs2230444
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_001291694.2(NR2C2):c.1578G>A(p.Gln526=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 1,613,676 control chromosomes in the GnomAD database, including 6,219 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.072 ( 432 hom., cov: 32)
Exomes 𝑓: 0.084 ( 5787 hom. )
Consequence
NR2C2
NM_001291694.2 synonymous
NM_001291694.2 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.41
Genes affected
NR2C2 (HGNC:7972): (nuclear receptor subfamily 2 group C member 2) This gene encodes a protein that belongs to the nuclear hormone receptor family. Members of this family act as ligand-activated transcription factors and function in many biological processes such as development, cellular differentiation and homeostasis. The activated receptor/ligand complex is translocated to the nucleus where it binds to hormone response elements of target genes. The protein encoded by this gene plays a role in protecting cells from oxidative stress and damage induced by ionizing radiation. The lack of a similar gene in mouse results in growth retardation, severe spinal curvature, subfertility, premature aging, and prostatic intraepithelial neoplasia (PIN) development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014]
MRPS25 (HGNC:14511): (mitochondrial ribosomal protein S25) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein. A pseudogene corresponding to this gene is found on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP7
?
Synonymous conserved (PhyloP=2.41 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0907 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NR2C2 | NM_001291694.2 | c.1578G>A | p.Gln526= | synonymous_variant | 13/14 | ENST00000425241.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NR2C2 | ENST00000425241.6 | c.1578G>A | p.Gln526= | synonymous_variant | 13/14 | 2 | NM_001291694.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0717 AC: 10909AN: 152058Hom.: 434 Cov.: 32
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GnomAD3 exomes AF: 0.0655 AC: 16454AN: 251268Hom.: 715 AF XY: 0.0669 AC XY: 9080AN XY: 135806
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GnomAD4 exome AF: 0.0843 AC: 123184AN: 1461500Hom.: 5787 Cov.: 31 AF XY: 0.0832 AC XY: 60526AN XY: 727084
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GnomAD4 genome ? AF: 0.0717 AC: 10913AN: 152176Hom.: 432 Cov.: 32 AF XY: 0.0678 AC XY: 5044AN XY: 74414
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Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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