2-174575327-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001375834.1(WIPF1):c.235G>A(p.Gly79Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_001375834.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WIPF1 | NM_001375834.1 | c.235G>A | p.Gly79Arg | missense_variant | 4/8 | ENST00000679041.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WIPF1 | ENST00000679041.1 | c.235G>A | p.Gly79Arg | missense_variant | 4/8 | NM_001375834.1 | P3 | ||
ENST00000454203.1 | n.101C>T | non_coding_transcript_exon_variant | 1/2 | 3 | |||||
ENST00000442996.1 | n.217+27850C>T | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000105 AC: 26AN: 248258Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 134488
GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461658Hom.: 0 Cov.: 32 AF XY: 0.0000880 AC XY: 64AN XY: 727124
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74426
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 12, 2023 | The c.235G>A (p.G79R) alteration is located in exon 4 (coding exon 3) of the WIPF1 gene. This alteration results from a G to A substitution at nucleotide position 235, causing the glycine (G) at amino acid position 79 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Wiskott-Aldrich syndrome 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 79 of the WIPF1 protein (p.Gly79Arg). This variant is present in population databases (rs531744802, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with WIPF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 540143). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at