10-86467457-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015045.5(WAPL):​c.2192G>A​(p.Arg731His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

WAPL
NM_015045.5 missense

Scores

11
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
WAPL (HGNC:23293): (WAPL cohesin release factor) Involved in several processes, including negative regulation of DNA replication; negative regulation of chromatin binding activity; and regulation of sister chromatid cohesion. Located in several cellular components, including Golgi apparatus; intercellular bridge; and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.823

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WAPLNM_015045.5 linkc.2192G>A p.Arg731His missense_variant Exon 9 of 19 ENST00000298767.10 NP_055860.1 Q7Z5K2-1A8K273B2RTX8
WAPLNM_001318328.2 linkc.2174G>A p.Arg725His missense_variant Exon 9 of 19 NP_001305257.1 Q7Z5K2A8K273B2RTX8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WAPLENST00000298767.10 linkc.2192G>A p.Arg731His missense_variant Exon 9 of 19 1 NM_015045.5 ENSP00000298767.4 Q7Z5K2-1
WAPLENST00000372075.2 linkc.50G>A p.Arg17His missense_variant Exon 1 of 10 2 ENSP00000361145.2 F6QZY1
WAPLENST00000489996.1 linkn.242G>A non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

WAPL-related disorder Uncertain:1
Mar 08, 2018
Baylor Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.45
T;T;.
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
.;D;D
M_CAP
Benign
0.038
D
MetaRNN
Pathogenic
0.82
D;D;D
MetaSVM
Benign
-0.35
T
MutationAssessor
Uncertain
2.3
M;M;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.5
D;.;.
REVEL
Uncertain
0.41
Sift
Uncertain
0.0070
D;.;.
Sift4G
Pathogenic
0.0
D;D;.
Polyphen
1.0
D;D;.
Vest4
0.80
MutPred
0.61
Loss of phosphorylation at S728 (P = 0.1089);Loss of phosphorylation at S728 (P = 0.1089);.;
MVP
0.47
MPC
3.2
ClinPred
0.99
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.63
gMVP
0.72

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: rs1564570621; hg19: chr10-88227214; COSMIC: COSV53932214; API