chr5-2748872-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_033267.5(IRX2):c.836C>T(p.Pro279Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000181 in 1,593,036 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P279S) has been classified as Uncertain significance.
Frequency
Consequence
NM_033267.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRX2 | NM_033267.5 | c.836C>T | p.Pro279Leu | missense_variant | 3/4 | ENST00000302057.6 | |
IRX2 | NM_001134222.2 | c.836C>T | p.Pro279Leu | missense_variant | 3/5 | ||
IRX2 | XM_011513979.3 | c.836C>T | p.Pro279Leu | missense_variant | 3/5 | ||
IRX2 | XM_024454379.2 | c.557C>T | p.Pro186Leu | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRX2 | ENST00000302057.6 | c.836C>T | p.Pro279Leu | missense_variant | 3/4 | 1 | NM_033267.5 | P1 | |
IRX2 | ENST00000382611.10 | c.836C>T | p.Pro279Leu | missense_variant | 3/5 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000276 AC: 42AN: 152104Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.000177 AC: 38AN: 214710Hom.: 0 AF XY: 0.000175 AC XY: 21AN XY: 119916
GnomAD4 exome AF: 0.000171 AC: 247AN: 1440816Hom.: 0 Cov.: 32 AF XY: 0.000174 AC XY: 125AN XY: 717032
GnomAD4 genome AF: 0.000276 AC: 42AN: 152220Hom.: 1 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74426
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 05, 2024 | The c.836C>T (p.P279L) alteration is located in exon 3 (coding exon 3) of the IRX2 gene. This alteration results from a C to T substitution at nucleotide position 836, causing the proline (P) at amino acid position 279 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at