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GeneBe

rs878853252

chr1-8361236-C-CCCTGGAGGAGCTGAGGAGGGAG

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_001042681.2(RERE):c.2270_2271insCTCCCTCCTCAGCTCCTCCAGG(p.Thr758SerfsTer36) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 33)

Consequence

RERE
NM_001042681.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.76
Variant links:
Genes affected
RERE (HGNC:9965): (arginine-glutamic acid dipeptide repeats) This gene encodes a member of the atrophin family of arginine-glutamic acid (RE) dipeptide repeat-containing proteins. The encoded protein co-localizes with a transcription factor in the nucleus, and its overexpression triggers apoptosis. A similar protein in mouse associates with histone deacetylase and is thought to function as a transcriptional co-repressor during embryonic development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1
?
    PVS1 - null variant (nonsense, frameshift, canonical ±1 or 2 splice sites, initiation codon, single or multiexon deletion) in a gene where LOF is a known mechanism of disease
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
PP5
?
    PP5 - Reputable source recently reports variant as pathogenic, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-8361236-C-CCCTGGAGGAGCTGAGGAGGGAG is Pathogenic according to our data. Variant chr1-8361236-C-CCCTGGAGGAGCTGAGGAGGGAG is described in ClinVar as [Pathogenic]. Clinvar id is 236219.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RERENM_001042681.2 linkuse as main transcriptc.2270_2271insCTCCCTCCTCAGCTCCTCCAGG p.Thr758SerfsTer36 frameshift_variant 18/23 ENST00000400908.7
RERENM_001042682.2 linkuse as main transcriptc.608_609insCTCCCTCCTCAGCTCCTCCAGG p.Thr204SerfsTer36 frameshift_variant 8/13
RERENM_012102.4 linkuse as main transcriptc.2270_2271insCTCCCTCCTCAGCTCCTCCAGG p.Thr758SerfsTer36 frameshift_variant 19/24

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
REREENST00000400908.7 linkuse as main transcriptc.2270_2271insCTCCCTCCTCAGCTCCTCCAGG p.Thr758SerfsTer36 frameshift_variant 18/231 NM_001042681.2 P1Q9P2R6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33
GnomAD4 exome
Cov.:
34
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMJan 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs878853252; hg19: chr1-8421296; API