rs769736838
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001013838.3(CARMIL2):āc.2672A>Cā(p.Gln891Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,348 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 (ā ā ).
Frequency
Consequence
NM_001013838.3 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 |
---|---|---|---|---|---|---|---|
CARMIL2 | NM_001013838.3 | c.2672A>C | p.Gln891Pro | missense_variant | 26/38 | ENST00000334583.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARMIL2 | ENST00000334583.11 | c.2672A>C | p.Gln891Pro | missense_variant | 26/38 | 1 | NM_001013838.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000562 AC: 14AN: 248926Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135150
GnomAD4 exome AF: 0.0000773 AC: 113AN: 1461140Hom.: 0 Cov.: 32 AF XY: 0.0000881 AC XY: 64AN XY: 726842
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74362
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 | Jul 13, 2015 | The p.Gln891Pro variant in RLTPR has not been previously reported, but was ident ified in 7/66280 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computational prediction tools and conservatio n analyses suggest that the variant may not impact the protein, though this info rmation is not predictive enough to rule out pathogenicity. In summary, the clin ical significance of the p.Gln891Pro variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 10, 2022 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 891 of the CARMIL2 protein (p.Gln891Pro). This variant is present in population databases (rs769736838, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CARMIL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 229203). 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"). 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