Variant rs10887621 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_015045.5(WAPL):c.370G>T(p.Val124Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000626 in 1,614,014 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V124I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 2 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 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=0.0048210025).

BS2

High AC in GnomAd4 at 84 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WAPL	NM_015045.5 linkuse as main transcript	c.370G>T	p.Val124Phe	missense_variant	2/19	ENST00000298767.10	NP_055860.1	Q7Z5K2-1A8K273B2RTX8
WAPL	NM_001318328.2 linkuse as main transcript	c.370G>T	p.Val124Phe	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>T	p.Val124Phe	missense_variant	2/19	1	NM_015045.5	ENSP00000298767.4		Q7Z5K2-1

Frequencies

GnomAD3 genomes

AF:

0.000546

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000735

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00112

AC:

282

AN:

251340

Hom.:

AF XY:

0.00112

AC XY:

152

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00278

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000880

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.000633

AC:

926

AN:

1461840

Hom.:

Cov.:

AF XY:

0.000679

AC XY:

494

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00257

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000520

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.000552

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000735

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.0000369

Hom.:

12219

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.00123

AC:

149

EpiCase

AF:

0.00185

EpiControl

AF:

0.00172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.079

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.69

.;T

M_CAP

Benign

0.0071

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.45

N;.

REVEL

Benign

0.033

Sift

Benign

0.032

D;.

Sift4G

Benign

0.36

T;T

Polyphen

0.031

B;B

Vest4

0.11

MVP

0.043

MPC

0.23

ClinPred

0.010

GERP RS

1.1

Varity_R

0.076

gMVP

0.21

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