chr8-107901346-GAAT-G

Position:

• chr8-107901346-GAAT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_178565.5(RSPO2):​c.617-159_617-157del 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPO2	NM_178565.5	c.617-159_617-157del		intron_variant		ENST00000276659.10
RSPO2	NM_001282863.2	c.425-159_425-157del		intron_variant
RSPO2	NM_001317942.2	c.416-159_416-157del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPO2	ENST00000276659.10	c.617-159_617-157del		intron_variant		1	NM_178565.5	P1
	ENST00000665144.1	n.81-16814_81-16812del		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0795

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.0491

Gnomad4 SAS AF: 0.0560

Gnomad4 FIN AF: 0.0554

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0430

Bravo AF: 0.0409

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs35321772; hg19: chr8-108913574;