Variant X-16947078-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004726.3(REPS2):c.217G>A(p.Gly73Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000547 in 1,075,348 control chromosomes in the GnomAD database, including 3 homozygotes. There are 174 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00045 ( 0 hom., 19 hem., cov: 21)

Exomes 𝑓: 0.00056 ( 3 hom. 155 hem. )

Consequence

REPS2
NM_004726.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.09

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007565856).

BP6

Variant X-16947078-G-A is Benign according to our data. Variant chrX-16947078-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 726618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
REPS2	NM_004726.3 linkuse as main transcript	c.217G>A	p.Gly73Ser	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.217G>A	p.Gly73Ser	missense_variant	1/18	1	NM_004726.3	ENSP00000349824.3	Q8NFH8-1
REPS2	ENST00000303843.7 linkuse as main transcript	c.217G>A	p.Gly73Ser	missense_variant	1/18	1		ENSP00000306033.7	Q8NFH8-4
REPS2	ENST00000481792.1 linkuse as main transcript	n.9G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.000453

AC:

AN:

110467

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

AN XY:

32809

show subpopulations

Gnomad AFR

AF:

0.0000327

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000375

Gnomad FIN

AF:

0.00191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000707

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000533

AC:

AN:

54436

Hom.:

AF XY:

0.000328

AC XY:

AN XY:

12188

show subpopulations

Gnomad AFR exome

AF:

0.000519

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00239

Gnomad NFE exome

AF:

0.000793

Gnomad OTH exome

AF:

0.00139

GnomAD4 exome

AF:

0.000558

AC:

538

AN:

964881

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

155

AN XY:

303883

show subpopulations

Gnomad4 AFR exome

AF:

0.0000478

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000284

Gnomad4 FIN exome

AF:

0.00155

Gnomad4 NFE exome

AF:

0.000591

Gnomad4 OTH exome

AF:

0.000675

GnomAD4 genome

AF:

0.000453

AC:

AN:

110467

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

AN XY:

32809

show subpopulations

Gnomad4 AFR

AF:

0.0000327

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000375

Gnomad4 FIN

AF:

0.00191

Gnomad4 NFE

AF:

0.000707

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000332

ExAC

AF:

0.000513

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.016

T;.

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.63

T;T

MetaRNN

Benign

0.0076

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.060

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.048

Sift

Benign

0.73

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.10

B;B

Vest4

0.10

MVP

0.43

MPC

0.38

ClinPred

0.023

GERP RS

2.3

Varity_R

0.078

gMVP

0.26

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