10-86453799-T-C

Variant names:

• chr10-86453799-T-C
• NM_015045.5:c.2690A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015045.5(WAPL):​c.2690A>G​(p.Gln897Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.75

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07973102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAPL	NM_015045.5	c.2690A>G	p.Gln897Arg	missense_variant	Exon 13 of 19	ENST00000298767.10	NP_055860.1
WAPL	NM_001318328.2	c.2672A>G	p.Gln891Arg	missense_variant	Exon 13 of 19		NP_001305257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAPL	ENST00000298767.10	c.2690A>G	p.Gln897Arg	missense_variant	Exon 13 of 19	1	NM_015045.5	ENSP00000298767.4
WAPL	ENST00000372075.2	c.548A>G	p.Gln183Arg	missense_variant	Exon 5 of 10	2		ENSP00000361145.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2690A>G (p.Q897R) alteration is located in exon 13 (coding exon 12) of the WAPL gene. This alteration results from a A to G substitution at nucleotide position 2690, causing the glutamine (Q) at amino acid position 897 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	18
DANN	Benign	0.19
DEOGEN2	Benign	0.068	T;T;T;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.4	N;N;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.34	N;.;N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;.;T;T
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.0	B;B;.;.
Vest4		0.097
MutPred		0.53		Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);.;.;
MVP		0.043
MPC		0.57
ClinPred		0.24	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-88213556;