chr12-118036424-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_018639.5(WSB2):​c.747C>T​(p.Pro249Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000402 in 1,614,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00040 ( 0 hom. )

Consequence

WSB2
NM_018639.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -7.58
Variant links:
Genes affected
WSB2 (HGNC:19222): (WD repeat and SOCS box containing 2) This gene encodes a member of the WD-protein subfamily. The encoded protein contains five WD-repeats spanning most of the protein and an SOCS box in the C-terminus. The SOCS box may act as a bridge between specific substrate-binding domains and E3 ubiquitin protein ligases. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2013]
RFC5 (HGNC:9973): (replication factor C subunit 5) This gene encodes the smallest subunit of the replication factor C complex, which consists of five distinct subunits (140, 40, 38, 37, and 36 kDa) and is required for DNA replication. This subunit interacts with the C-terminal region of proliferating cell nuclear antigen and is required to open and load proliferating cell nuclear antigen onto DNA during S phase. It is a member of the AAA+ (ATPases associated with various cellular activities) ATPase family and forms a core complex with the 38 and 40 kDa subunits that possesses DNA-dependent ATPase activity. A related pseudogene has been identified on chromosome 9. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 12-118036424-G-A is Benign according to our data. Variant chr12-118036424-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643378.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-7.58 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WSB2NM_018639.5 linkc.747C>T p.Pro249Pro synonymous_variant Exon 6 of 9 ENST00000315436.8 NP_061109.1 Q9NYS7-1
WSB2NM_001278557.1 linkc.798C>T p.Pro266Pro synonymous_variant Exon 6 of 9 NP_001265486.1 Q9NYS7-2
WSB2NM_001278558.2 linkc.117C>T p.Pro39Pro synonymous_variant Exon 4 of 7 NP_001265487.1 Q9NYS7-3
RFC5XR_007063112.1 linkn.1665-1449G>A intron_variant Intron 12 of 12

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WSB2ENST00000315436.8 linkc.747C>T p.Pro249Pro synonymous_variant Exon 6 of 9 1 NM_018639.5 ENSP00000319474.3 Q9NYS7-1

Frequencies

GnomAD3 genomes
AF:
0.000381
AC:
58
AN:
152168
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000603
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000477
AC:
120
AN:
251468
Hom.:
0
AF XY:
0.000530
AC XY:
72
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000781
Gnomad ASJ exome
AF:
0.00109
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000633
Gnomad OTH exome
AF:
0.000814
GnomAD4 exome
AF:
0.000404
AC:
591
AN:
1461876
Hom.:
0
Cov.:
30
AF XY:
0.000450
AC XY:
327
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000939
Gnomad4 ASJ exome
AF:
0.00119
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000408
Gnomad4 OTH exome
AF:
0.000662
GnomAD4 genome
AF:
0.000381
AC:
58
AN:
152286
Hom.:
0
Cov.:
32
AF XY:
0.000322
AC XY:
24
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000603
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000409
Hom.:
0
Bravo
AF:
0.000548

ClinVar

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

Submissions by phenotype

not provided Benign:1
Jun 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

WSB2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.70
CADD
Benign
0.22
DANN
Benign
0.91
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

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

Other links and lift over

dbSNP: rs147184268; hg19: chr12-118474229; API