5-138444447-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001271803.2(REEP2):​c.215T>G​(p.Phe72Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Consequence

REEP2
NM_001271803.2 missense

Scores

13
5
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.98
Variant links:
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 Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.929

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
REEP2NM_001271803.2 linkc.215T>G p.Phe72Cys missense_variant Exon 4 of 8 ENST00000378339.7 NP_001258732.1 Q9BRK0-2A8K3D2
REEP2NM_016606.4 linkc.215T>G p.Phe72Cys missense_variant Exon 4 of 8 NP_057690.2 Q9BRK0-1A8K3D2
REEP2NR_073448.2 linkn.442T>G non_coding_transcript_exon_variant Exon 4 of 8
REEP2NR_073449.2 linkn.442T>G non_coding_transcript_exon_variant Exon 4 of 8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
REEP2ENST00000378339.7 linkc.215T>G p.Phe72Cys missense_variant Exon 4 of 8 1 NM_001271803.2 ENSP00000367590.2 Q9BRK0-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.54
D
BayesDel_noAF
Pathogenic
0.54
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.89
.;D;.;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D;D;D;D
M_CAP
Pathogenic
0.34
D
MetaRNN
Pathogenic
0.93
D;D;D;D
MetaSVM
Uncertain
0.39
D
MutationAssessor
Pathogenic
4.1
H;H;.;.
PrimateAI
Pathogenic
0.91
D
PROVEAN
Pathogenic
-8.0
D;D;D;.
REVEL
Pathogenic
0.96
Sift
Pathogenic
0.0
D;D;D;.
Sift4G
Pathogenic
0.0010
D;D;D;D
Polyphen
0.97
.;D;.;.
Vest4
0.88
MutPred
0.78
Gain of ubiquitination at K69 (P = 0.1047);Gain of ubiquitination at K69 (P = 0.1047);.;.;
MVP
0.99
MPC
2.1
ClinPred
1.0
D
GERP RS
5.1
Varity_R
0.93
gMVP
0.97

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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: rs483352925; hg19: chr5-137780136; API