5-138441242-C-T

Variant names:

• chr5-138441242-C-T
• rs2269947
• NM_001271803.2:c.106-143C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001271803.2(REEP2):​c.106-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,256,162 control chromosomes in the GnomAD database, including 95,691 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8561 hom., cov: 32)
  • Exomes 𝑓: 0.39 (87130 hom.)
• Consequence: REEP2 NM_001271803.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.464
• Publications: 11 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 5-138441242-C-T is Benign according to our data. Variant chr5-138441242-C-T is described in ClinVar as Benign. ClinVar VariationId is 1295465.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

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.106-143C>T		intron	N/A	NP_001258732.1	Q9BRK0-2
	REEP2	NM_016606.4		c.106-143C>T		intron	N/A	NP_057690.2
	REEP2	NR_073448.2		n.333-143C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP2	ENST00000378339.7	TSL:1 MANE Select	c.106-143C>T		intron	N/A	ENSP00000367590.2	Q9BRK0-2
	REEP2	ENST00000254901.9	TSL:1	c.106-143C>T		intron	N/A	ENSP00000254901.5	Q9BRK0-1
	REEP2	ENST00000903314.1		c.106-143C>T		intron	N/A	ENSP00000573373.1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48789 AN: 151952 Hom.: 8550 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.305

GnomAD4 exome AF: 0.389 AC: 429094 AN: 1104092 Hom.: 87130 Cov.: 15 AF XY: 0.396 AC XY: 221832 AN XY: 560612

African (AFR) AF: 0.198 AC: 5292 AN: 26674

American (AMR) AF: 0.213 AC: 8671 AN: 40718

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 7367 AN: 22172

East Asian (EAS) AF: 0.267 AC: 10032 AN: 37546

South Asian (SAS) AF: 0.549 AC: 41108 AN: 74922

European-Finnish (FIN) AF: 0.334 AC: 15850 AN: 47404

Middle Eastern (MID) AF: 0.345 AC: 1627 AN: 4722

European-Non Finnish (NFE) AF: 0.401 AC: 321573 AN: 801530

Other (OTH) AF: 0.363 AC: 17574 AN: 48404

GnomAD4 genome AF: 0.321 AC: 48818 AN: 152070 Hom.: 8561 Cov.: 32 AF XY: 0.319 AC XY: 23702 AN XY: 74348

African (AFR) AF: 0.203 AC: 8416 AN: 41478

American (AMR) AF: 0.252 AC: 3855 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1195 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5182

South Asian (SAS) AF: 0.535 AC: 2579 AN: 4824

European-Finnish (FIN) AF: 0.326 AC: 3448 AN: 10572

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27082 AN: 67940

Other (OTH) AF: 0.303 AC: 638 AN: 2106

Alfa AF: 0.347 Hom.: 14159

Bravo AF: 0.304

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.3
DANN	Benign	0.28
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs2269947; hg19: chr5-137776931; COSMIC: COSV107389142; COSMIC: COSV107389142;