Variant X-16947130-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004726.3(REPS2):c.269A>G(p.His90Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

REPS2
NM_004726.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.94

Variant links:

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]

REPS2 links:

REPS2 (HGNC:):

REPS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20252225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REPS2	NM_004726.3 linkuse as main transcript	c.269A>G	p.His90Arg	missense_variant	1/18	ENST00000357277.8	NP_004717.2	Q8NFH8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
REPS2	ENST00000357277.8 linkuse as main transcript	c.269A>G	p.His90Arg	missense_variant	1/18	1	NM_004726.3	ENSP00000349824.3	Q8NFH8-1
REPS2	ENST00000303843.7 linkuse as main transcript	c.269A>G	p.His90Arg	missense_variant	1/18	1		ENSP00000306033.7	Q8NFH8-4
REPS2	ENST00000481792.1 linkuse as main transcript	n.61A>G		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

969337

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

301625

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.269A>G (p.H90R) alteration is located in exon 1 (coding exon 1) of the REPS2 gene. This alteration results from a A to G substitution at nucleotide position 269, causing the histidine (H) at amino acid position 90 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.025

T;.

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.068

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.13

N;N

REVEL

Benign

0.068

Sift

Benign

0.64

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.14

B;P

Vest4

0.35

MutPred

0.45

Loss of catalytic residue at L89 (P = 0.1811);Loss of catalytic residue at L89 (P = 0.1811);

MVP

0.65

MPC

0.64

ClinPred

0.23

GERP RS

2.4

Varity_R

0.086

gMVP

0.60

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over