rs372043866
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBS1_Supporting
The NM_004448.4(ERBB2):c.3689G>A(p.Arg1230Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. R1230L) has been classified as Uncertain significance.
Frequency
Consequence
NM_004448.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ERBB2 | NM_004448.4 | c.3689G>A | p.Arg1230Gln | missense_variant | 27/27 | ENST00000269571.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ERBB2 | ENST00000269571.10 | c.3689G>A | p.Arg1230Gln | missense_variant | 27/27 | 1 | NM_004448.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249482Hom.: 0 AF XY: 0.0000443 AC XY: 6AN XY: 135292
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461394Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727058
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74344
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 28, 2023 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1230 of the ERBB2 protein (p.Arg1230Gln). This variant is present in population databases (rs372043866, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ERBB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2169413). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at