chr21-33243687-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_001289125.3(IFNAR2):c.70G>A(p.Val24Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,613,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001289125.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFNAR2 | NM_001289125.3 | c.70G>A | p.Val24Met | missense_variant | 3/9 | ENST00000342136.9 | |
IFNAR2-IL10RB | NM_001414505.1 | c.70G>A | p.Val24Met | missense_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFNAR2 | ENST00000342136.9 | c.70G>A | p.Val24Met | missense_variant | 3/9 | 1 | NM_001289125.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251394Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135878
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461196Hom.: 0 Cov.: 29 AF XY: 0.0000248 AC XY: 18AN XY: 726978
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152248Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74440
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 03, 2023 | The c.70G>A (p.V24M) alteration is located in exon 3 (coding exon 2) of the IFNAR2 gene. This alteration results from a G to A substitution at nucleotide position 70, causing the valine (V) at amino acid position 24 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with IFNAR2-related conditions. This variant is present in population databases (rs561488102, gnomAD 0.1%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 24 of the IFNAR2 protein (p.Val24Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at