Variant 10-86517700-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBA1

The NM_015045.5(WAPL):c.370G>A(p.Val124Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,613,938 control chromosomes in the GnomAD database, including 58,339 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.21 ( 4021 hom., cov: 33)

Exomes 𝑓: 0.27 ( 54318 hom. )

Consequence

WAPL
NM_015045.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

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]

WAPL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WAPL. . Gene score misZ 3.4597 (greater than the threshold 3.09). Trascript score misZ 4.2731 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038123429).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WAPL	NM_015045.5 linkuse as main transcript	c.370G>A	p.Val124Ile	missense_variant	2/19	ENST00000298767.10	NP_055860.1	Q7Z5K2-1A8K273B2RTX8
WAPL	NM_001318328.2 linkuse as main transcript	c.370G>A	p.Val124Ile	missense_variant	2/19		NP_001305257.1	Q7Z5K2A8K273B2RTX8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WAPL	ENST00000298767.10 linkuse as main transcript	c.370G>A	p.Val124Ile	missense_variant	2/19	1	NM_015045.5	ENSP00000298767.4		Q7Z5K2-1

Frequencies

GnomAD3 genomes

AF:

0.212

AC:

32204

AN:

152014

Hom.:

4022

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0940

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.127

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.304

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.174

GnomAD3 exomes

AF:

0.241

AC:

60653

AN:

251340

Hom.:

8259

AF XY:

0.253

AC XY:

34423

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0946

Gnomad AMR exome

AF:

0.0996

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.193

Gnomad SAS exome

AF:

0.351

Gnomad FIN exome

AF:

0.290

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.228

GnomAD4 exome

AF:

0.267

AC:

389965

AN:

1461806

Hom.:

54318

Cov.:

AF XY:

0.270

AC XY:

196679

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0898

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.251

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.350

Gnomad4 FIN exome

AF:

0.293

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.247

GnomAD4 genome

AF:

0.212

AC:

32203

AN:

152132

Hom.:

4021

Cov.:

AF XY:

0.214

AC XY:

15884

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0938

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.244

Gnomad4 EAS

AF:

0.198

Gnomad4 SAS

AF:

0.339

Gnomad4 FIN

AF:

0.304

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.256

Hom.:

12219

Bravo

AF:

0.189

TwinsUK

AF:

0.272

AC:

1007

ALSPAC

AF:

0.278

AC:

1073

ESP6500AA

AF:

0.105

AC:

462

ESP6500EA

AF:

0.282

AC:

2426

ExAC

AF:

0.247

AC:

30049

EpiCase

AF:

0.262

EpiControl

AF:

0.255

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.075

T;T

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.46

.;T

MetaRNN

Benign

0.0038

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.11

N;.

REVEL

Benign

0.080

Sift

Benign

0.089

T;.

Sift4G

Benign

0.40

T;T

Polyphen

0.014

B;B

Vest4

0.012

MPC

0.14

ClinPred

0.0013

GERP RS

1.1

Varity_R

0.033

gMVP

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over