2-86214989-CA-C

Position:

• chr2-86214989-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001371279.1(REEP1):​c.*2049del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0048 (2 hom., cov: 0)
  • Exomes 𝑓: 0.039 (0 hom.)
• Consequence: REEP1 NM_001371279.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.227

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-86214989-CA-C is Benign according to our data. Variant chr2-86214989-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1190594.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00484 (447/92282) while in subpopulation AFR AF= 0.0211 (375/17804). AF 95% confidence interval is 0.0193. There are 2 homozygotes in gnomad4. There are 226 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REEP1	NM_001371279.1	c.*2049del		3_prime_UTR_variant	9/9	ENST00000538924.7	NP_001358208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REEP1	ENST00000538924.7	c.*2049del		3_prime_UTR_variant	9/9	5	NM_001371279.1	ENSP00000438346

Frequencies

GnomAD3 genomes AF: 0.00482 AC: 445 AN: 92268 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000373

Gnomad EAS AF: 0.000244

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00307

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000758

Gnomad OTH AF: 0.00233

GnomAD4 exome AF: 0.0391 AC: 9 AN: 230 Hom.: 0 Cov.: 0 AF XY: 0.0448 AC XY: 6 AN XY: 134

Gnomad4 FIN exome AF: 0.0354

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.00484 AC: 447 AN: 92282 Hom.: 2 Cov.: 0 AF XY: 0.00524 AC XY: 226 AN XY: 43170

Gnomad4 AFR AF: 0.0211

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000373

Gnomad4 EAS AF: 0.000245

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00307

Gnomad4 NFE AF: 0.000758

Gnomad4 OTH AF: 0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs200132323; hg19: chr2-86442112;