rs10887621

Variant names:

• chr10-86517700-C-A
• rs10887621
• NM_015045.5:c.370G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-86517700-C-A
• chr10-86517700-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00063 (2 hom.)
• Consequence: WAPL NM_015045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 24 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048210025).
• BS2: High AC in GnomAd4 at 84 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015045.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAPL	NM_015045.5	MANE Select	c.370G>T	p.Val124Phe	missense	Exon 2 of 19	NP_055860.1
	WAPL	NM_001318328.2		c.370G>T	p.Val124Phe	missense	Exon 2 of 19	NP_001305257.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAPL	ENST00000298767.10	TSL:1 MANE Select	c.370G>T	p.Val124Phe	missense	Exon 2 of 19	ENSP00000298767.4

Frequencies

GnomAD3 genomes AF: 0.000546 AC: 83 AN: 152056 Hom.: 0 Cov.: 33

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

GnomAD2 exomes AF: 0.00112 AC: 282 AN: 251340 AF XY: 0.00112

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 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.: 2 Cov.: 36 AF XY: 0.000679 AC XY: 494 AN XY: 727218

African (AFR) AF: 0.0000896 AC: 3 AN: 33480

American (AMR) AF: 0.00257 AC: 115 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000957 AC: 25 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00125 AC: 108 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00607 AC: 35 AN: 5766

European-Non Finnish (NFE) AF: 0.000520 AC: 578 AN: 1111996

Other (OTH) AF: 0.00103 AC: 62 AN: 60394

GnomAD4 genome AF: 0.000552 AC: 84 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39 AN XY: 74392

African (AFR) AF: 0.0000241 AC: 1 AN: 41546

American (AMR) AF: 0.000785 AC: 12 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 67990

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.0000249 Hom.: 17394

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.00123 AC: 149

EpiCase AF: 0.00185

EpiControl AF: 0.00172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.033
Sift	Benign	0.032	D
Sift4G	Benign	0.36	T
Polyphen		0.031	B
Vest4		0.11
MVP		0.043
MPC		0.23
ClinPred		0.010	T
GERP RS		1.1
Varity_R		0.076
gMVP		0.21
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs10887621; hg19: chr10-88277457;