rs2006847

Positions:

• chrX-17068772-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004726.3(REPS2):​c.1279+301G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 111,567 control chromosomes in the GnomAD database, including 7,775 homozygotes. There are 14,336 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (7775 hom., 14336 hem., cov: 23)
• Consequence: REPS2 NM_004726.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

Genes affected

REPS2 (HGNC:9963): (RALBP1 associated Eps domain containing 2) The product of this gene is part of a protein complex that regulates the endocytosis of growth factor receptors. The encoded protein directly interacts with a GTPase activating protein that functions downstream of the small G protein Ral. Its expression can negatively affect receptor internalization and inhibit growth factor signaling. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REPS2	NM_004726.3	c.1279+301G>A		intron_variant		ENST00000357277.8	NP_004717.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REPS2	ENST00000357277.8	c.1279+301G>A		intron_variant		1	NM_004726.3	ENSP00000349824.3
REPS2	ENST00000303843.7	c.1276+301G>A		intron_variant		1		ENSP00000306033.7

Frequencies

GnomAD3 genomes AF: 0.435 AC: 48509 AN: 111513 Hom.: 7771 Cov.: 23 AF XY: 0.424 AC XY: 14305 AN XY: 33741

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.553

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.418

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 48544 AN: 111567 Hom.: 7775 Cov.: 23 AF XY: 0.424 AC XY: 14336 AN XY: 33805

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.390

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.420

Alfa AF: 0.436 Hom.: 5665

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.65

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: rs2006847; hg19: chrX-17086895; COSMIC: COSV58185975;