Variant rs758888137 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The ENST00000276659.10(RSPO2):c.205C>T(p.Arg69Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,611,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

RSPO2
ENST00000276659.10 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.41

Variant links:

Genes affected

RSPO2 (HGNC:28583): (R-spondin 2) This gene encodes a member of the R-spondin family of proteins. These proteins are secreted ligands of leucine-rich repeat containing G protein-coupled receptors that enhance Wnt signaling through the inhibition of ubiquitin E3 ligases. A chromosomal translocation including this locus that results in the formation of a gene fusion has been identified in multiple human cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

RSPO2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.839

PP5

Variant 8-107989134-G-A is Pathogenic according to our data. Variant chr8-107989134-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 545634.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RSPO2	NM_178565.5 linkuse as main transcript	c.205C>T	p.Arg69Cys	missense_variant	3/6	ENST00000276659.10	NP_848660.3
RSPO2	NM_001317942.2 linkuse as main transcript	c.4C>T	p.Arg2Cys	missense_variant	2/5		NP_001304871.1
RSPO2	NM_001282863.2 linkuse as main transcript	c.95-28317C>T		intron_variant			NP_001269792.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO2	ENST00000276659.10 linkuse as main transcript	c.205C>T	p.Arg69Cys	missense_variant	3/6	1	NM_178565.5	ENSP00000276659	P1	Q6UXX9-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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:

0.00000411

AC:

AN:

1459768

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726230

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152026

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Humerofemoral hypoplasia with radiotibial ray deficiency

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 18, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.84

.;D;.;.;.;.;.

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;.;.;D;.;D

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.84

D;D;D;D;D;D;D

MetaSVM

Uncertain

0.20

MutationAssessor

Uncertain

2.3

.;M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-6.7

D;D;D;D;D;D;D

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;.;.;.

Polyphen

1.0

.;D;.;.;.;.;.

Vest4

0.90

MutPred

0.48

.;Loss of MoRF binding (P = 0.0322);.;.;Loss of MoRF binding (P = 0.0322);.;Loss of MoRF binding (P = 0.0322);

MVP

0.67

MPC

0.70

ClinPred

1.0

GERP RS

2.9

Varity_R

0.71

gMVP

0.57

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