5-2748377-C-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_033267.5(IRX2):āc.1331G>Cā(p.Arg444Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000195 in 1,468,542 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 33)
Exomes š: 0.00021 ( 1 hom. )
Consequence
IRX2
NM_033267.5 missense
NM_033267.5 missense
Scores
1
9
8
Clinical Significance
Conservation
PhyloP100: 5.86
Genes affected
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAd4 at 17 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRX2 | NM_033267.5 | c.1331G>C | p.Arg444Pro | missense_variant | 3/4 | ENST00000302057.6 | |
IRX2 | NM_001134222.2 | c.1331G>C | p.Arg444Pro | missense_variant | 3/5 | ||
IRX2 | XM_011513979.3 | c.1331G>C | p.Arg444Pro | missense_variant | 3/5 | ||
IRX2 | XM_024454379.2 | c.1052G>C | p.Arg351Pro | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRX2 | ENST00000302057.6 | c.1331G>C | p.Arg444Pro | missense_variant | 3/4 | 1 | NM_033267.5 | P1 | |
IRX2 | ENST00000382611.10 | c.1331G>C | p.Arg444Pro | missense_variant | 3/5 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 151968Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
17
AN:
151968
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000221 AC: 17AN: 76840Hom.: 0 AF XY: 0.000272 AC XY: 12AN XY: 44188
GnomAD3 exomes
AF:
AC:
17
AN:
76840
Hom.:
AF XY:
AC XY:
12
AN XY:
44188
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000205 AC: 270AN: 1316574Hom.: 1 Cov.: 32 AF XY: 0.000242 AC XY: 157AN XY: 648768
GnomAD4 exome
AF:
AC:
270
AN:
1316574
Hom.:
Cov.:
32
AF XY:
AC XY:
157
AN XY:
648768
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000112 AC: 17AN: 151968Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6AN XY: 74240
GnomAD4 genome
AF:
AC:
17
AN:
151968
Hom.:
Cov.:
33
AF XY:
AC XY:
6
AN XY:
74240
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
4
Asia WGS
AF:
AC:
1
AN:
3468
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2022 | The c.1331G>C (p.R444P) alteration is located in exon 3 (coding exon 3) of the IRX2 gene. This alteration results from a G to C substitution at nucleotide position 1331, causing the arginine (R) at amino acid position 444 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MutPred
Loss of methylation at R444 (P = 0.0286);Loss of methylation at R444 (P = 0.0286);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at