rs766962416
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_198576.4(AGRN):c.6022G>A(p.Ala2008Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 1,405,554 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A2008A) has been classified as Likely benign.
Frequency
Consequence
NM_198576.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGRN | NM_198576.4 | c.6022G>A | p.Ala2008Thr | missense_variant | 36/36 | ENST00000379370.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGRN | ENST00000379370.7 | c.6022G>A | p.Ala2008Thr | missense_variant | 36/36 | 1 | NM_198576.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000548 AC: 9AN: 164116Hom.: 0 AF XY: 0.0000797 AC XY: 7AN XY: 87858
GnomAD4 exome AF: 0.0000178 AC: 25AN: 1405554Hom.: 0 Cov.: 31 AF XY: 0.0000274 AC XY: 19AN XY: 694474
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Congenital myasthenic syndrome 8 Uncertain:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect, ClinGen | - | Variant interpretted as Uncertain significance and reported on 02-08-2018 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2018 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AGRN-related disease. This variant is present in population databases (rs766962416, ExAC 0.03%). This sequence change replaces alanine with threonine at codon 2008 of the AGRN protein (p.Ala2008Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at