rs1348470

Positions:

• chr8-107997664-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_178565.5(RSPO2):​c.95-8420T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0304 in 152,308 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.030 (195 hom., cov: 33)
• Consequence: RSPO2 NM_178565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.09 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO2	NM_178565.5	c.95-8420T>C		intron_variant		ENST00000276659.10	NP_848660.3
RSPO2	NM_001282863.2	c.95-36847T>C		intron_variant			NP_001269792.1
RSPO2	NM_001317942.2	c.-107-8420T>C		intron_variant			NP_001304871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO2	ENST00000276659.10	c.95-8420T>C		intron_variant		1	NM_178565.5	ENSP00000276659	P1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4612 AN: 152192 Hom.: 191 Cov.: 33

Gnomad AFR AF: 0.0923

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0679

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.0229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0304 AC: 4630 AN: 152308 Hom.: 195 Cov.: 33 AF XY: 0.0307 AC XY: 2289 AN XY: 74484

Gnomad4 AFR AF: 0.0924

Gnomad4 AMR AF: 0.0145

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.000376

Gnomad4 NFE AF: 0.00178

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0170 Hom.: 7

Bravo AF: 0.0339

Asia WGS AF: 0.0520 AC: 180 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs1348470; hg19: chr8-109009892;