5-138439254-C-A

Variant names:

• chr5-138439254-C-A
• rs1204384058
• NM_001271803.2:c.32+14C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001271803.2(REEP2):​c.32+14C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,265,886 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000016 (1 hom.)
• Consequence: REEP2 NM_001271803.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.838
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

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.32+14C>A		intron	N/A	NP_001258732.1	Q9BRK0-2
	REEP2	NM_016606.4		c.32+14C>A		intron	N/A	NP_057690.2
	REEP2	NR_073448.2		n.184+14C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP2	ENST00000378339.7	TSL:1 MANE Select	c.32+14C>A		intron	N/A	ENSP00000367590.2	Q9BRK0-2
	REEP2	ENST00000254901.9	TSL:1	c.32+14C>A		intron	N/A	ENSP00000254901.5	Q9BRK0-1
	REEP2	ENST00000903314.1		c.32+14C>A		intron	N/A	ENSP00000573373.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000158 AC: 2 AN: 1265886 Hom.: 1 Cov.: 30 AF XY: 0.00000325 AC XY: 2 AN XY: 615766

African (AFR) AF: 0.00 AC: 0 AN: 25730

American (AMR) AF: 0.00 AC: 0 AN: 21186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17690

East Asian (EAS) AF: 0.00 AC: 0 AN: 31864

South Asian (SAS) AF: 0.00 AC: 0 AN: 52150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4536

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1018854

Other (OTH) AF: 0.0000389 AC: 2 AN: 51400

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	17
DANN	Benign	0.96
PhyloP100		0.84
PromoterAI		-0.048	Neutral

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

Other links and lift over

dbSNP: rs1204384058; hg19: chr5-137774943;