1-208027296-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_025179.4(PLXNA2):c.5632C>T(p.Arg1878Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000171 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R1878Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_025179.4 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PLXNA2 | NM_025179.4 | c.5632C>T | p.Arg1878Trp | missense_variant | 32/32 | ENST00000367033.4 | NP_079455.3 | |
PLXNA2 | XM_005273164.4 | c.5872C>T | p.Arg1958Trp | missense_variant | 33/33 | XP_005273221.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PLXNA2 | ENST00000367033.4 | c.5632C>T | p.Arg1878Trp | missense_variant | 32/32 | 1 | NM_025179.4 | ENSP00000356000.3 | ||
PLXNA2 | ENST00000483048.1 | n.1668C>T | non_coding_transcript_exon_variant | 3/3 | 1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249124Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134850
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461186Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 726946
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 18, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1878 of the PLXNA2 protein (p.Arg1878Trp). This variant is present in population databases (rs141651654, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with PLXNA2-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PLXNA2 protein function. 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. - |
PLXNA2-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 29, 2024 | The PLXNA2 c.5632C>T variant is predicted to result in the amino acid substitution p.Arg1878Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at