8-107901346-GAATAAT-GAAT

Variant names:

• chr8-107901346-GAAT-G
• rs35321772
• NM_178565.5:c.617-159_617-157delATT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178565.5(RSPO2):​c.617-159_617-157delATT variant causes a intron change. The variant allele was found at a frequency of 0.0421 in 152,194 control chromosomes in the GnomAD database, including 178 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.042 (178 hom., cov: 32)
• Consequence: RSPO2 NM_178565.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.75
• 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• tetraamelia-multiple malformations syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287949 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-107901346-GAAT-G is Benign according to our data. Variant chr8-107901346-GAAT-G is described in ClinVar as Benign. ClinVar VariationId is 1270815.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0772 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO2	NM_178565.5	MANE Select	c.617-159_617-157delATT		intron	N/A	NP_848660.3
	RSPO2	NM_001282863.2		c.425-159_425-157delATT		intron	N/A	NP_001269792.1	Q6UXX9-3
	RSPO2	NM_001317942.2		c.416-159_416-157delATT		intron	N/A	NP_001304871.1	Q6UXX9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO2	ENST00000276659.10	TSL:1 MANE Select	c.617-159_617-157delATT		intron	N/A	ENSP00000276659.5	Q6UXX9-1
	RSPO2	ENST00000517781.5	TSL:1	c.425-159_425-157delATT		intron	N/A	ENSP00000427937.1	Q6UXX9-3
	RSPO2	ENST00000517939.5	TSL:1	c.416-159_416-157delATT		intron	N/A	ENSP00000428940.1	Q6UXX9-2

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6398 AN: 152076 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.0490

Gnomad SAS AF: 0.0562

Gnomad FIN AF: 0.0554

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0421 AC: 6404 AN: 152194 Hom.: 178 Cov.: 32 AF XY: 0.0431 AC XY: 3204 AN XY: 74388

African (AFR) AF: 0.0795 AC: 3301 AN: 41516

American (AMR) AF: 0.0238 AC: 364 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3470

East Asian (EAS) AF: 0.0491 AC: 254 AN: 5170

South Asian (SAS) AF: 0.0560 AC: 270 AN: 4822

European-Finnish (FIN) AF: 0.0554 AC: 586 AN: 10584

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0197 AC: 1343 AN: 68018

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0339 Hom.: 15

Bravo AF: 0.0409

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.8
Mutation Taster		=98/2	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: rs35321772; hg19: chr8-108913574;