10-86517698-AAC-GAA

Variant names:

• chr10-86517698-AAC-GAA
• NM_015045.5:c.370_372delGTTinsTTC
• WAPL p.Val124Phe

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_015045.5(WAPL):​c.370_372delGTTinsTTC​(p.Val124Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WAPL NM_015045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.52
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAPL	NM_015045.5	MANE Select	c.370_372delGTTinsTTC	p.Val124Phe	missense	N/A	NP_055860.1	Q7Z5K2-1
	WAPL	NM_001318328.2		c.370_372delGTTinsTTC	p.Val124Phe	missense	N/A	NP_001305257.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WAPL	ENST00000298767.10	TSL:1 MANE Select	c.370_372delGTTinsTTC	p.Val124Phe	missense	N/A	ENSP00000298767.4	Q7Z5K2-1
	WAPL	ENST00000920312.1		c.370_372delGTTinsTTC	p.Val124Phe	missense	N/A	ENSP00000590371.1
	WAPL	ENST00000910171.1		c.370_372delGTTinsTTC	p.Val124Phe	missense	N/A	ENSP00000580230.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-88277455;