rs1811446926

Variant names:

• chr8-107901141-C-G
• NM_178565.5:c.666G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-107901141-C-G
• chr8-107901141-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_178565.5(RSPO2):​c.666G>C​(p.Arg222Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: RSPO2 NM_178565.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504

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]

ENSG00000287949 (HGNC:):

ACMG classification

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=0.09391597).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPO2	NM_178565.5	c.666G>C	p.Arg222Ser	missense_variant	Exon 6 of 6	ENST00000276659.10	NP_848660.3
RSPO2	NM_001282863.2	c.474G>C	p.Arg158Ser	missense_variant	Exon 5 of 5		NP_001269792.1
RSPO2	NM_001317942.2	c.465G>C	p.Arg155Ser	missense_variant	Exon 5 of 5		NP_001304871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPO2	ENST00000276659.10	c.666G>C	p.Arg222Ser	missense_variant	Exon 6 of 6	1	NM_178565.5	ENSP00000276659.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461786 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727182

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000224

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;.;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.85	T;T;T;.
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.094	T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.34	.;.;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N;N;N;N
REVEL	Benign	0.19
Sift	Uncertain	0.0090	D;D;D;D
Sift4G	Benign	0.34	T;T;T;T
Polyphen		0.0070, 0.069	.;B;B;.
Vest4		0.20
MutPred		0.18		.;.;Gain of phosphorylation at R222 (P = 0.0152);.;
MVP		0.36
MPC		0.16
ClinPred		0.34	T
GERP RS		3.2
Varity_R		0.18
gMVP		0.16

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.

Other links and lift over

hg19: chr8-108913369;