Variant chr8-107958108-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_178565.5(RSPO2):c.588C>T(p.Cys196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,613,338 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 11 hom. )

Consequence

RSPO2
NM_178565.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.23

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 8-107958108-G-A is Benign according to our data. Variant chr8-107958108-G-A is described in ClinVar as [Benign]. Clinvar id is 716774.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.23 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RSPO2	NM_178565.5 linkuse as main transcript	c.588C>T	p.Cys196=	synonymous_variant	5/6	ENST00000276659.10
RSPO2	NM_001282863.2 linkuse as main transcript	c.396C>T	p.Cys132=	synonymous_variant	4/5
RSPO2	NM_001317942.2 linkuse as main transcript	c.387C>T	p.Cys129=	synonymous_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPO2	ENST00000276659.10 linkuse as main transcript	c.588C>T	p.Cys196=	synonymous_variant	5/6	1	NM_178565.5	P1	Q6UXX9-1
	ENST00000665144.1 linkuse as main transcript	n.326-1102G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00424

AC:

644

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00233

AC:

585

AN:

250884

Hom.:

AF XY:

0.00232

AC XY:

314

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.0135

Gnomad AMR exome

AF:

0.00136

Gnomad ASJ exome

AF:

0.00725

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.0000926

Gnomad NFE exome

AF:

0.00172

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00146

AC:

2126

AN:

1461162

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1058

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.0124

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.00678

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.000187

Gnomad4 NFE exome

AF:

0.00107

Gnomad4 OTH exome

AF:

0.00278

GnomAD4 genome

AF:

0.00425

AC:

646

AN:

152176

Hom.:

Cov.:

AF XY:

0.00413

AC XY:

307

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0115

Gnomad4 AMR

AF:

0.00249

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00312

Hom.:

Bravo

AF:

0.00505

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00224

EpiControl

AF:

0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 14, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.7

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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