rs483352924

chr5-138441091-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_001271803.2(REEP2):c.105+3G>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: REEP2 NM_001271803.2 splice_donor_region, intron
• Scores: Splicing: ADA: 0.9993
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.05

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 5-138441091-G-T is Pathogenic according to our data. Variant chr5-138441091-G-T is described in ClinVar as [Pathogenic]. Clinvar id is 97003.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP2	NM_001271803.2	c.105+3G>T		splice_donor_region_variant, intron_variant		ENST00000378339.7
REEP2	NM_016606.4	c.105+3G>T		splice_donor_region_variant, intron_variant
REEP2	NR_073448.2	n.332+3G>T		splice_donor_region_variant, intron_variant, non_coding_transcript_variant
REEP2	NR_073449.2	n.332+3G>T		splice_donor_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP2	ENST00000378339.7	c.105+3G>T		splice_donor_region_variant, intron_variant		1	NM_001271803.2	A1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spastic paraplegia 72b, autosomal recessive Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 06, 2014

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
Cadd	Benign	21
Dann	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.86
SpliceAI score (max)		0.63		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.63		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs483352924; hg19: chr5-137776780;