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

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]

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
REEP1	NM_001371279.1	c.-39_-35dupAGCCG		5_prime_UTR_variant	Exon 1 of 9	ENST00000538924.7	NP_001358208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
REEP1	ENST00000538924.7	c.-39_-35dupAGCCG		5_prime_UTR_variant	Exon 1 of 9	5	NM_001371279.1	ENSP00000438346.3

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

Gnomad4 AFR exome AF: 0.153 AC: 3327 AN: 21698

Gnomad4 AMR exome AF: 0.00834 AC: 71 AN: 8512

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 13076

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 23846

Gnomad4 SAS exome AF: 0.000313 AC: 8 AN: 25528

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 26682

Gnomad4 NFE exome AF: 0.000457 AC: 421 AN: 921572

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.151 AC: 0.151211 AN: 0.151211

Gnomad4 AMR AF: 0.0153 AC: 0.0152576 AN: 0.0152576

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.000622 AC: 0.000621633 AN: 0.000621633

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000594 AC: 0.000593683 AN: 0.000593683

Gnomad4 OTH AF: 0.0263 AC: 0.026341 AN: 0.026341

Alfa AF: 0.0385 Hom.: 14

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Jul 19, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 31, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is found in MITONUC-MITOP panel(s). -

Spastic paraplegia, autosomal dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs544099237; hg19: chr2-86564667;