2-86337544-GCGGCT-GCGGCTCGGCT

Variant names:

• chr2-86337544-G-GCGGCT
• rs544099237
• NM_001371279.1:c.-39_-35dupAGCCG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001371279.1(REEP1):​c.-39_-35dupAGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00874 in 1,236,372 control chromosomes in the GnomAD database, including 759 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (487 hom., cov: 31)
  • Exomes 𝑓: 0.0039 (272 hom.)
• Consequence: REEP1 NM_001371279.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.468
• Publications: 1 publications found

Genes affected

REEP1 (HGNC:25786): (receptor accessory protein 1) This gene encodes a mitochondrial protein that functions to enhance the cell surface expression of odorant receptors. Mutations in this gene cause spastic paraplegia autosomal dominant type 31, a neurodegenerative disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

REEP1 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 31

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• neuronopathy, distal hereditary motor, type 5B

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• neuronopathy, distal hereditary motor, type 5A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• spinal muscular atrophy, distal, autosomal recessive, 6

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 2-86337544-G-GCGGCT is Benign according to our data. Variant chr2-86337544-G-GCGGCT is described in ClinVar as Benign. ClinVar VariationId is 337388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371279.1. 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
	REEP1	NM_001371279.1	MANE Select	c.-39_-35dupAGCCG		5_prime_UTR	Exon 1 of 9	NP_001358208.1
	REEP1	NM_001410855.1		c.-39_-35dupAGCCG		5_prime_UTR	Exon 1 of 8	NP_001397784.1
	REEP1	NM_001410856.1		c.-39_-35dupAGCCG		5_prime_UTR	Exon 1 of 8	NP_001397785.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	REEP1	ENST00000538924.7	TSL:5 MANE Select	c.-39_-35dupAGCCG		5_prime_UTR	Exon 1 of 9	ENSP00000438346.3
	REEP1	ENST00000165698.9	TSL:1	c.-39_-35dupAGCCG		5_prime_UTR	Exon 1 of 7	ENSP00000165698.5
	REEP1	ENST00000908467.1		c.-39_-35dupAGCCG		5_prime_UTR	Exon 1 of 9	ENSP00000578526.1

Frequencies

GnomAD3 genomes AF: 0.0436 AC: 6557 AN: 150320 Hom.: 485 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0153

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000594

Gnomad OTH AF: 0.0266

GnomAD2 exomes AF: 0.00408 AC: 29 AN: 7110 AF XY: 0.00300

Gnomad AFR exome AF: 0.0453

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000498

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00390 AC: 4239 AN: 1085946 Hom.: 272 Cov.: 30 AF XY: 0.00350 AC XY: 1829 AN XY: 522366

African (AFR) AF: 0.153 AC: 3327 AN: 21698

American (AMR) AF: 0.00834 AC: 71 AN: 8512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13076

East Asian (EAS) AF: 0.00 AC: 0 AN: 23846

South Asian (SAS) AF: 0.000313 AC: 8 AN: 25528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26682

Middle Eastern (MID) AF: 0.00848 AC: 24 AN: 2830

European-Non Finnish (NFE) AF: 0.000457 AC: 421 AN: 921572

Other (OTH) AF: 0.00919 AC: 388 AN: 42202

GnomAD4 genome AF: 0.0437 AC: 6573 AN: 150426 Hom.: 487 Cov.: 31 AF XY: 0.0418 AC XY: 3074 AN XY: 73498

African (AFR) AF: 0.151 AC: 6242 AN: 41280

American (AMR) AF: 0.0153 AC: 231 AN: 15140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5138

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9922

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000594 AC: 40 AN: 67376

Other (OTH) AF: 0.0263 AC: 55 AN: 2088

Alfa AF: 0.0385 Hom.: 14

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Spastic paraplegia, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47
Mutation Taster		=300/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs544099237; hg19: chr2-86564667;