rs483352925

Variant names:

• chr5-138444447-T-A
• rs483352925
• NM_001271803.2:c.215T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-138444447-T-A
• chr5-138444447-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_001271803.2(REEP2):​c.215T>A​(p.Phe72Tyr) 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. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: REEP2 NM_001271803.2 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.919
• PP5: Variant 5-138444447-T-A is Pathogenic according to our data. Variant chr5-138444447-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 97004.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP2	NM_001271803.2	c.215T>A	p.Phe72Tyr	missense_variant	Exon 4 of 8	ENST00000378339.7	NP_001258732.1
REEP2	NM_016606.4	c.215T>A	p.Phe72Tyr	missense_variant	Exon 4 of 8		NP_057690.2
REEP2	NR_073448.2	n.442T>A		non_coding_transcript_exon_variant	Exon 4 of 8
REEP2	NR_073449.2	n.442T>A		non_coding_transcript_exon_variant	Exon 4 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP2	ENST00000378339.7	c.215T>A	p.Phe72Tyr	missense_variant	Exon 4 of 8	1	NM_001271803.2	ENSP00000367590.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spastic paraplegia 72b, autosomal recessive Pathogenic:1

Feb 06, 2014

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	29
DANN	Uncertain	1.0
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	0.47	D
MetaRNN	Pathogenic	0.92	D;D;D;D
MetaSVM	Uncertain	0.39	D
MutationAssessor	Pathogenic	4.1	H;H;.;.
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-3.0	D;D;D;.
REVEL	Pathogenic	0.97
Sift	Uncertain	0.0010	D;D;D;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		1.0	.;D;.;.
Vest4		0.90
MutPred		0.75		Loss of stability (P = 0.0879);Loss of stability (P = 0.0879);.;.;
MVP		0.96
MPC		1.8
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.83
gMVP		0.90

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

Other links and lift over

dbSNP: rs483352925; hg19: chr5-137780136;