Variant chrX-16946875-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004726.3(REPS2):c.14C>T(p.Ala5Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 740,136 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000099 ( 0 hom., 1 hem., cov: 20)

Exomes 𝑓: 0.000011 ( 0 hom. 1 hem. )

Consequence

REPS2
NM_004726.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.17

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0870325).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REPS2	NM_004726.3 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/18	ENST00000357277.8	NP_004717.2	Q8NFH8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
REPS2	ENST00000357277.8 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/18	1	NM_004726.3	ENSP00000349824.3		Q8NFH8-1
REPS2	ENST00000303843.7 linkuse as main transcript	c.14C>T	p.Ala5Val	missense_variant	1/18	1		ENSP00000306033.7		Q8NFH8-4

Frequencies

GnomAD3 genomes

AF:

0.00000994

AC:

AN:

100632

Hom.:

Cov.:

AF XY:

0.0000367

AC XY:

AN XY:

27230

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000323

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

639504

Hom.:

Cov.:

AF XY:

0.00000532

AC XY:

AN XY:

187916

show subpopulations

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:

0.0000120

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000994

AC:

AN:

100632

Hom.:

Cov.:

AF XY:

0.0000367

AC XY:

AN XY:

27230

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000323

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 30, 2023

The c.14C>T (p.A5V) alteration is located in exon 1 (coding exon 1) of the REPS2 gene. This alteration results from a C to T substitution at nucleotide position 14, causing the alanine (A) at amino acid position 5 to be replaced by a valine (V). 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

Uncertain

0.41

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.025

T;.

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.087

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.082

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.15

T;T

Polyphen

0.038

B;B

Vest4

0.19

MutPred

0.28

Gain of catalytic residue at A5 (P = 0.0155);Gain of catalytic residue at A5 (P = 0.0155);

MVP

0.16

MPC

0.38

ClinPred

0.083

GERP RS

1.0

Varity_R

0.12

gMVP

0.43

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over