11-36593690-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000536.4(RAG2):c.479C>T(p.Ser160Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S160S) has been classified as Likely benign.
Frequency
Consequence
NM_000536.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAG2 | NM_000536.4 | c.479C>T | p.Ser160Leu | missense_variant | 2/2 | ENST00000311485.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAG2 | ENST00000311485.8 | c.479C>T | p.Ser160Leu | missense_variant | 2/2 | 1 | NM_000536.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 250980Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135638
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461856Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727240
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152176Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2013 | The S160L missense change represents a non-conservative amino acid substitution, as a polar Serine residue is replaced with a non-polar Leucine residue. This substitution occurs at a highly conserved position in RAG2 and is located in the core region of the protein, which is responsible for catalytic function. Therefore, S160L is a strong candidate for a pathogenic variant, which is further strengthened by the presence of the novel R73C mutation on the opposite allele in this particular individual. However, the possibility that S160L is a benign variant cannot be excluded. - |
Inborn error of immunity;C2700553:Histiocytic medullary reticulosis;CN257931:Recombinase activating gene 2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Pediatric Immunology Service, The Chaim Sheba Medical Center at Tel HaShomer | Mar 06, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at