chr18-35005550-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_StrongBS2
The NM_001143827.3(MAPRE2):āc.83C>Gā(p.Ser28Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,540,218 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 (ā ).
Frequency
Genomes: š 0.000046 ( 0 hom., cov: 32)
Exomes š: 0.000038 ( 0 hom. )
Consequence
MAPRE2
NM_001143827.3 stop_gained
NM_001143827.3 stop_gained
Scores
2
3
2
Clinical Significance
Conservation
PhyloP100: 1.31
Genes affected
MAPRE2 (HGNC:6891): (microtubule associated protein RP/EB family member 2) The protein encoded by this gene shares significant homology to the adenomatous polyposis coli (APC) protein-binding EB1 gene family. This protein is a microtubule-associated protein that is necessary for spindle symmetry during mitosis. It is thought to play a role in the tumorigenesis of colorectal cancers and the proliferative control of normal cells. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 11 pathogenic variants in the truncated region.
BS2
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MAPRE2 | NM_001143827.3 | c.83C>G | p.Ser28Ter | stop_gained | 2/8 | ||
MAPRE2 | NM_001143826.3 | c.-11C>G | 5_prime_UTR_variant | 2/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MAPRE2 | ENST00000436190.6 | c.83C>G | p.Ser28Ter | stop_gained | 2/8 | 2 | |||
MAPRE2 | ENST00000413393.5 | c.-11C>G | 5_prime_UTR_variant | 2/8 | 5 | P4 | |||
MAPRE2 | ENST00000587359.5 | c.-11C>G | 5_prime_UTR_variant | 3/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152084Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000382 AC: 53AN: 1388134Hom.: 0 Cov.: 28 AF XY: 0.0000467 AC XY: 32AN XY: 684558
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74276
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 11, 2021 | Loss of function has not been clearly established as a mechanism of disease. May escape nonsense-mediated mRNA decay and/or be rescued by re-initiation. This region of the MAPRE2 gene is excluded from other highly expressed transcript isoforms. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
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Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
MutationTaster
Benign
A;D
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at