chr4-184408172-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_002199.4(IRF2):c.515C>T(p.Thr172Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000877 in 1,595,958 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Consequence
IRF2
NM_002199.4 missense
NM_002199.4 missense
Scores
2
15
2
Clinical Significance
Conservation
PhyloP100: 4.91
Genes affected
IRF2 (HGNC:6117): (interferon regulatory factor 2) IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta, and presumably other genes that employ IRF1 for transcription activation. However, IRF2 also functions as a transcriptional activator of histone H4. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF2 | NM_002199.4 | c.515C>T | p.Thr172Met | missense_variant | 6/9 | ENST00000393593.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF2 | ENST00000393593.8 | c.515C>T | p.Thr172Met | missense_variant | 6/9 | 1 | NM_002199.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251266Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135802
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GnomAD4 exome AF: 0.00000900 AC: 13AN: 1443816Hom.: 0 Cov.: 27 AF XY: 0.0000111 AC XY: 8AN XY: 719724
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74316
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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 17, 2023 | The c.515C>T (p.T172M) alteration is located in exon 6 (coding exon 5) of the IRF2 gene. This alteration results from a C to T substitution at nucleotide position 515, causing the threonine (T) at amino acid position 172 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Uncertain
D;.
Polyphen
P;.
Vest4
MutPred
Loss of glycosylation at T172 (P = 0.1022);Loss of glycosylation at T172 (P = 0.1022);
MVP
MPC
ClinPred
D
GERP RS
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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