NM_015045.5:c.2708A>G

Variant names:

• chr10-86453781-T-C
• NM_015045.5:c.2708A>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.2708A>G​(p.Asp903Gly) 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. 13/21 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: 5.96

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=0.18766713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAPL	NM_015045.5	c.2708A>G	p.Asp903Gly	missense_variant	Exon 13 of 19	ENST00000298767.10	NP_055860.1
WAPL	NM_001318328.2	c.2690A>G	p.Asp897Gly	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.2708A>G	p.Asp903Gly	missense_variant	Exon 13 of 19	1	NM_015045.5	ENSP00000298767.4
WAPL	ENST00000372075.2	c.566A>G	p.Asp189Gly	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

Feb 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2708A>G (p.D903G) 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 2708, causing the aspartic acid (D) at amino acid position 903 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T;T;.
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.080
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N;N;.;.
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.83	N;.;N;.
REVEL	Benign	0.079
Sift	Benign	0.041	D;.;T;.
Sift4G	Benign	0.15	T;T;T;.
Polyphen		0.011	B;B;.;.
Vest4		0.18
MutPred		0.49		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);.;.;
MVP		0.12
MPC		0.75
ClinPred		0.76	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-88213538;