Variant 5-138439209-A-G details in Genebe, Genetics Data Aggregator

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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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]

REEP2 links:

REEP2 (HGNC:):

REEP2 links:

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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	Protein	UniProt
REEP2	NM_001271803.2 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/8	ENST00000378339.7	NP_001258732.1	Q9BRK0-2A8K3D2
REEP2	NM_016606.4 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/8		NP_057690.2	Q9BRK0-1A8K3D2
REEP2	NR_073448.2 linkuse as main transcript	n.153A>G		non_coding_transcript_exon_variant	1/8
REEP2	NR_073449.2 linkuse as main transcript	n.153A>G		non_coding_transcript_exon_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP2	ENST00000378339.7 linkuse as main transcript	c.1A>G	p.Met1?	start_lost	1/8	1	NM_001271803.2	ENSP00000367590.2		Q9BRK0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000163

AC:

AN:

1227510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

600266

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000200

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Labcorp Genetics (formerly Invitae), Labcorp

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.48

BayesDel_noAF

Pathogenic

0.45

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

.;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

D;D

M_CAP

Pathogenic

0.99

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Uncertain

0.55

PROVEAN

Benign

-2.3

N;D

REVEL

Pathogenic

0.87

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.59

.;P

Vest4

0.89

MutPred

0.98

Loss of disorder (P = 0.1031);Loss of disorder (P = 0.1031);

MVP

0.94

ClinPred

0.99

GERP RS

4.3

Varity_R

0.60

gMVP

0.89

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over