rs9297407

Variant names:

• chr8-107997446-A-G
• rs9297407
• NM_178565.5:c.95-8202T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_178565.5(RSPO2):​c.95-8202T>C variant causes a intron change. The variant allele was found at a frequency of 0.104 in 152,192 control chromosomes in the GnomAD database, including 2,089 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 0.10 (2089 hom., cov: 32)
• Consequence: RSPO2 NM_178565.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.35
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• tetraamelia syndrome 2

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178565.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO2	NM_178565.5	MANE Select	c.95-8202T>C		intron	N/A	NP_848660.3
	RSPO2	NM_001282863.2		c.95-36629T>C		intron	N/A	NP_001269792.1
	RSPO2	NM_001317942.2		c.-107-8202T>C		intron	N/A	NP_001304871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO2	ENST00000276659.10	TSL:1 MANE Select	c.95-8202T>C		intron	N/A	ENSP00000276659.5
	RSPO2	ENST00000517781.5	TSL:1	c.95-36629T>C		intron	N/A	ENSP00000427937.1
	RSPO2	ENST00000517939.5	TSL:1	c.-107-8202T>C		intron	N/A	ENSP00000428940.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15792 AN: 152074 Hom.: 2087 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0442

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.0430

Gnomad FIN AF: 0.0247

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.104 AC: 15807 AN: 152192 Hom.: 2089 Cov.: 32 AF XY: 0.100 AC XY: 7481 AN XY: 74440

African (AFR) AF: 0.313 AC: 12978 AN: 41458

American (AMR) AF: 0.0440 AC: 673 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3472

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5178

South Asian (SAS) AF: 0.0428 AC: 207 AN: 4832

European-Finnish (FIN) AF: 0.0247 AC: 262 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0191 AC: 1296 AN: 68024

Other (OTH) AF: 0.0787 AC: 166 AN: 2110

Alfa AF: 0.0530 Hom.: 281

Bravo AF: 0.114

Asia WGS AF: 0.0370 AC: 128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Benign	0.84
PhyloP100		5.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9297407; hg19: chr8-109009674;