5-138440951-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001271803.2(REEP2):c.33-65G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0085 in 1,604,184 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (13 hom., cov: 33)
  • Exomes 𝑓: 0.0087 (53 hom.)
• Consequence: REEP2 NM_001271803.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.650

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-138440951-G-A is Benign according to our data. Variant chr5-138440951-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1318089.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00646 (984/152278) while in subpopulation NFE AF= 0.0102 (692/68006). AF 95% confidence interval is 0.00955. There are 13 homozygotes in gnomad4. There are 465 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP2	NM_001271803.2	c.33-65G>A		intron_variant		ENST00000378339.7
REEP2	NM_016606.4	c.33-65G>A		intron_variant
REEP2	NR_073448.2	n.195G>A		non_coding_transcript_exon_variant	2/8
REEP2	NR_073449.2	n.195G>A		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP2	ENST00000378339.7	c.33-65G>A		intron_variant		1	NM_001271803.2	A1

Frequencies

GnomAD3 genomes AF: 0.00647 AC: 984 AN: 152160 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00871 AC: 12651 AN: 1451906 Hom.: 53 Cov.: 31 AF XY: 0.00851 AC XY: 6149 AN XY: 722600

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00410

Gnomad4 ASJ exome AF: 0.000576

Gnomad4 EAS exome AF: 0.000932

Gnomad4 SAS exome AF: 0.00218

Gnomad4 FIN exome AF: 0.0111

Gnomad4 NFE exome AF: 0.0102

Gnomad4 OTH exome AF: 0.00652

GnomAD4 genome AF: 0.00646 AC: 984 AN: 152278 Hom.: 13 Cov.: 33 AF XY: 0.00625 AC XY: 465 AN XY: 74450

Gnomad4 AFR AF: 0.00149

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00970

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00730 Hom.: 2

Bravo AF: 0.00591

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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

Apr 24, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	12
Dann	Benign	0.79

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: rs76951845; hg19: chr5-137776640;