chrX-14609137-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_002063.4(GLRA2):c.862G>A(p.Ala288Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,016 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Consequence
NM_002063.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLRA2 | NM_002063.4 | c.862G>A | p.Ala288Thr | missense_variant | 7/9 | ENST00000218075.9 | NP_002054.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLRA2 | ENST00000218075.9 | c.862G>A | p.Ala288Thr | missense_variant | 7/9 | 1 | NM_002063.4 | ENSP00000218075 | A1 | |
GLRA2 | ENST00000355020.9 | c.862G>A | p.Ala288Thr | missense_variant | 7/9 | 1 | ENSP00000347123 | P4 | ||
GLRA2 | ENST00000415367.2 | n.1113G>A | non_coding_transcript_exon_variant | 7/9 | 3 | |||||
GLRA2 | ENST00000443437.6 | c.*789G>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 2 | ENSP00000387756 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD4 exome AF: 9.18e-7 AC: 1AN: 1089016Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 355474
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
See cases Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Wangler Lab, Baylor College of Medicine | Jan 10, 2022 | Marcogliese et al., (2022) have identified 13 unrelated subjects with a variable neurodevelopmental disorder with or without autistic features. This variant (c.862C>G) results in p.Ile259Met. This change is not seen in GnomAD at this highly conserved position (PM2) and in silico models predict pathogenicity (PP3). We classify this variant to be likely pathogenic based on our cohort of affected individuals with similar phenotypes. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at