rs374810

Variant names:

• chr8-108083801-G-A
• rs374810
• ENST00000806167.1:n.319+155G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000806167.1(ENSG00000304773):​n.319+155G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,928 control chromosomes in the GnomAD database, including 12,789 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 0.40 (12789 hom., cov: 32)
• Consequence: ENSG00000304773 ENST00000806167.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 31 publications found

Genes affected

ENSG00000304773 (HGNC:):

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 Gene-Disease associations (from GenCC):

• tetraamelia syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• tetraamelia-multiple malformations syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000806167.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO2	NM_178565.5	MANE Select	c.-774C>T		upstream_gene	N/A	NP_848660.3
	RSPO2	NM_001282863.2		c.-1047C>T		upstream_gene	N/A	NP_001269792.1	Q6UXX9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000304773	ENST00000806167.1		n.319+155G>A		intron	N/A
	RSPO2	ENST00000276659.10	TSL:1 MANE Select	c.-774C>T		upstream_gene	N/A	ENSP00000276659.5	Q6UXX9-1
	RSPO2	ENST00000851102.1		c.-774C>T		upstream_gene	N/A	ENSP00000521161.1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 60098 AN: 151810 Hom.: 12779 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.469

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.494

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.396 AC: 60124 AN: 151928 Hom.: 12789 Cov.: 32 AF XY: 0.401 AC XY: 29790 AN XY: 74254

African (AFR) AF: 0.215 AC: 8922 AN: 41436

American (AMR) AF: 0.411 AC: 6277 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.469 AC: 1626 AN: 3468

East Asian (EAS) AF: 0.499 AC: 2555 AN: 5122

South Asian (SAS) AF: 0.516 AC: 2486 AN: 4814

European-Finnish (FIN) AF: 0.494 AC: 5209 AN: 10550

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31655 AN: 67948

Other (OTH) AF: 0.427 AC: 901 AN: 2108

Alfa AF: 0.440 Hom.: 41641

Bravo AF: 0.380

Asia WGS AF: 0.513 AC: 1786 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.4
DANN	Benign	0.64
PhyloP100		0.14
PromoterAI		-0.020	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374810; hg19: chr8-109096029;