5-138441137-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.105+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00979 in 1,610,122 control chromosomes in the GnomAD database, including 97 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (15 hom., cov: 33)
  • Exomes 𝑓: 0.010 (82 hom.)
• Consequence: REEP2 NM_001271803.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.697

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 5-138441137-G-A is Benign according to our data. Variant chr5-138441137-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00718 (1094/152352) while in subpopulation NFE AF= 0.0116 (788/68036). AF 95% confidence interval is 0.0109. There are 15 homozygotes in gnomad4. There are 517 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 15 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
REEP2	NM_001271803.2	c.105+49G>A		intron_variant		ENST00000378339.7
REEP2	NM_016606.4	c.105+49G>A		intron_variant
REEP2	NR_073448.2	n.332+49G>A		intron_variant, non_coding_transcript_variant
REEP2	NR_073449.2	n.332+49G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
REEP2	ENST00000378339.7	c.105+49G>A		intron_variant		1	NM_001271803.2	A1

Frequencies

GnomAD3 genomes AF: 0.00719 AC: 1094 AN: 152234 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00166

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.00595

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00664 AC: 1620 AN: 244130 Hom.: 4 AF XY: 0.00679 AC XY: 897 AN XY: 132128

Gnomad AFR exome AF: 0.00176

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.000506

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00211

Gnomad FIN exome AF: 0.00962

Gnomad NFE exome AF: 0.0104

Gnomad OTH exome AF: 0.00864

GnomAD4 exome AF: 0.0101 AC: 14677 AN: 1457770 Hom.: 82 Cov.: 30 AF XY: 0.00986 AC XY: 7150 AN XY: 725264

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00460

Gnomad4 ASJ exome AF: 0.000575

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.0111

Gnomad4 NFE exome AF: 0.0118

Gnomad4 OTH exome AF: 0.00779

GnomAD4 genome AF: 0.00718 AC: 1094 AN: 152352 Hom.: 15 Cov.: 33 AF XY: 0.00694 AC XY: 517 AN XY: 74500

Gnomad4 AFR AF: 0.00166

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00764 Hom.: 2

Bravo AF: 0.00659

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	6.4
Dann	Benign	0.71

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: rs184959604; hg19: chr5-137776826;