5-138439209-A-G
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_001271803.2(REEP2):c.1A>G(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000163 in 1,227,510 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 (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000016 ( 0 hom. )
Consequence
REEP2
NM_001271803.2 start_lost
NM_001271803.2 start_lost
Scores
5
8
2
Clinical Significance
Conservation
PhyloP100: 6.13
Genes affected
REEP2 (HGNC:17975): (receptor accessory protein 2) This gene encodes a member of the receptor expression enhancing protein family. Studies of a related gene in mouse suggest that the encoded protein is found in the cell membrane and enhances the function of sweet taste receptors. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
REEP2 | NM_001271803.2 | c.1A>G | p.Met1? | start_lost | 1/8 | ENST00000378339.7 | |
REEP2 | NM_016606.4 | c.1A>G | p.Met1? | start_lost | 1/8 | ||
REEP2 | NR_073448.2 | n.153A>G | non_coding_transcript_exon_variant | 1/8 | |||
REEP2 | NR_073449.2 | n.153A>G | non_coding_transcript_exon_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
REEP2 | ENST00000378339.7 | c.1A>G | p.Met1? | start_lost | 1/8 | 1 | NM_001271803.2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000163 AC: 2AN: 1227510Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 600266
GnomAD4 exome
AF:
AC:
2
AN:
1227510
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Cov.:
30
AF XY:
AC XY:
0
AN XY:
600266
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 72 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 26, 2020 | 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. Disruption of the initiator codon has been observed in individual(s) with autosomal recessive hereditary spastic paraplegia (PMID: 24482476). This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the REEP2 mRNA. The next in-frame methionine is located at codon 39. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D
PROVEAN
Benign
N;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
0.59
.;P
Vest4
MutPred
Loss of disorder (P = 0.1031);Loss of disorder (P = 0.1031);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.