rs779067650
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_020435.4(GJC2):c.1102G>A(p.Asp368Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,485,946 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_020435.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GJC2 | NM_020435.4 | c.1102G>A | p.Asp368Asn | missense_variant | 2/2 | ENST00000366714.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GJC2 | ENST00000366714.3 | c.1102G>A | p.Asp368Asn | missense_variant | 2/2 | 1 | NM_020435.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151704Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000106 AC: 1AN: 94328Hom.: 0 AF XY: 0.0000187 AC XY: 1AN XY: 53460
GnomAD4 exome AF: 0.0000142 AC: 19AN: 1334136Hom.: 0 Cov.: 33 AF XY: 0.0000106 AC XY: 7AN XY: 658426
GnomAD4 genome ? AF: 0.0000198 AC: 3AN: 151810Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74224
ClinVar
Submissions by phenotype
Spastic paraplegia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 05, 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 527981). This variant has not been reported in the literature in individuals affected with GJC2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 368 of the GJC2 protein (p.Asp368Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at