rs201383534
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016366.3(CABP2):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000849 in 1,555,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_016366.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CABP2 | NM_016366.3 | c.32G>A | p.Arg11Gln | missense_variant | 1/7 | ENST00000294288.5 | |
CABP2 | NM_001318496.2 | c.46G>A | p.Gly16Arg | missense_variant | 1/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CABP2 | ENST00000294288.5 | c.32G>A | p.Arg11Gln | missense_variant | 1/7 | 1 | NM_016366.3 | ||
CABP2 | ENST00000545205.2 | c.32G>A | p.Arg11Gln | missense_variant, NMD_transcript_variant | 1/7 | 1 | |||
CABP2 | ENST00000353903.9 | c.32G>A | p.Arg11Gln | missense_variant | 1/6 | 5 | P1 | ||
CABP2 | ENST00000636477.1 | c.165+917G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000194 AC: 31AN: 159708Hom.: 0 AF XY: 0.000189 AC XY: 16AN XY: 84684
GnomAD4 exome AF: 0.0000848 AC: 119AN: 1403280Hom.: 0 Cov.: 32 AF XY: 0.0000924 AC XY: 64AN XY: 692788
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74452
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 14, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Arg11Gln vari ant in CABP2 has not been previously reported in individuals with hearing loss, but has been identified in 0.2% (25/12534) of East Asian chromosomes by the Geno me Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs20138 3534). Computational prediction tools and conservation analysis suggest that thi s variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. While the clinical significance of the p.Arg11 Gln variant is uncertain, available evidence suggest that the p.Arg11Gln variant is more likely to be benign. ACMG/AMP Criteria applied: BP4. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces arginine with glutamine at codon 11 of the CABP2 protein (p.Arg11Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs201383534, ExAC 0.4%). This variant has not been reported in the literature in individuals affected with CABP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 517659). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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