8-107901196-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_178565.5(RSPO2):​c.617-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

RSPO2
NM_178565.5 splice_region, intron

Scores

2
Splicing: ADA: 0.00002503
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00700
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 8-107901196-A-G is Benign according to our data. Variant chr8-107901196-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3687619.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RSPO2NM_178565.5 linkc.617-6T>C splice_region_variant, intron_variant Intron 5 of 5 ENST00000276659.10 NP_848660.3 Q6UXX9-1B3KVP3
RSPO2NM_001282863.2 linkc.425-6T>C splice_region_variant, intron_variant Intron 4 of 4 NP_001269792.1 Q6UXX9-3
RSPO2NM_001317942.2 linkc.416-6T>C splice_region_variant, intron_variant Intron 4 of 4 NP_001304871.1 Q6UXX9-2B3KVP3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RSPO2ENST00000276659.10 linkc.617-6T>C splice_region_variant, intron_variant Intron 5 of 5 1 NM_178565.5 ENSP00000276659.5 Q6UXX9-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152072
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000422
AC:
1
AN:
236952
Hom.:
0
AF XY:
0.00000780
AC XY:
1
AN XY:
128218
show subpopulations
Gnomad AFR exome
AF:
0.0000636
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152072
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jun 13, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.49
DANN
Benign
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000025
dbscSNV1_RF
Benign
0.0040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs374633923; hg19: chr8-108913424; API