chr5-138441032-C-T

Variant names:

• chr5-138441032-C-T
• rs748834558
• NM_001271803.2:c.49C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001271803.2(REEP2):​c.49C>T​(p.Leu17Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: REEP2 NM_001271803.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.683
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 72

  Inheritance: AD, AR, SD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• hereditary spastic paraplegia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 5-138441032-C-T is Benign according to our data. Variant chr5-138441032-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3696614.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001271803.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP2	NM_001271803.2	MANE Select	c.49C>T	p.Leu17Leu	synonymous	Exon 2 of 8	NP_001258732.1	Q9BRK0-2
	REEP2	NM_016606.4		c.49C>T	p.Leu17Leu	synonymous	Exon 2 of 8	NP_057690.2
	REEP2	NR_073448.2		n.276C>T		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP2	ENST00000378339.7	TSL:1 MANE Select	c.49C>T	p.Leu17Leu	synonymous	Exon 2 of 8	ENSP00000367590.2	Q9BRK0-2
	REEP2	ENST00000254901.9	TSL:1	c.49C>T	p.Leu17Leu	synonymous	Exon 2 of 8	ENSP00000254901.5	Q9BRK0-1
	REEP2	ENST00000506158.5	TSL:2	c.-66C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 8	ENSP00000422530.1	B4DE60

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250610 AF XY: 0.00000738

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461176 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726922

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52746

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary spastic paraplegia 72 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs748834558; hg19: chr5-137776721; COSMIC: COSV99649725; COSMIC: COSV99649725;