chr2-211383664-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_005235.3(ERBB4):c.3878G>A(p.Gly1293Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,886 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 (★★).
Frequency
Consequence
NM_005235.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ERBB4 | ENST00000342788.9 | c.3878G>A | p.Gly1293Asp | missense_variant | Exon 28 of 28 | 1 | NM_005235.3 | ENSP00000342235.4 | ||
ERBB4 | ENST00000436443.5 | c.3830G>A | p.Gly1277Asp | missense_variant | Exon 27 of 27 | 1 | ENSP00000403204.1 | |||
ERBB4 | ENST00000260943.11 | c.3800G>A | p.Gly1267Asp | missense_variant | Exon 27 of 27 | 5 | ENSP00000260943.7 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251162Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135738
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461666Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727126
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74430
ClinVar
Submissions by phenotype
not provided Uncertain:1
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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with ERBB4-related conditions. This variant is present in population databases (rs545302445, gnomAD 0.0009%). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1293 of the ERBB4 protein (p.Gly1293Asp). -
Amyotrophic lateral sclerosis type 19 Uncertain:1
ACMG classification criteria: PM2 supporting -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at