rs886041068

Variant names:

• chr2-25743864-TG-T
• rs886041068
• NM_018263.6:c.2472delC

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_018263.6(ASXL2):​c.2472delC​(p.Ser825ValfsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ASXL2 NM_018263.6 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.808

Genes affected

ASXL2 (HGNC:23805): (ASXL transcriptional regulator 2) This gene encodes a member of a family of epigenetic regulators that bind various histone-modifying enzymes and are involved in the assembly of transcription factors at specific genomic loci. Naturally occurring mutations in this gene are associated with cancer in several tissue types (breast, bladder, pancreas, ovary, prostate, and blood). This gene plays an important role in neurodevelopment, cardiac function, adipogenesis, and osteoclastogenesis. [provided by RefSeq, Feb 2017]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.426 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-25743864-TG-T is Pathogenic according to our data. Variant chr2-25743864-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 268125.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL2	NM_018263.6	c.2472delC	p.Ser825ValfsTer16	frameshift_variant	Exon 13 of 13	ENST00000435504.9	NP_060733.4
ASXL2	NM_001369346.1	c.2298delC	p.Ser767ValfsTer16	frameshift_variant	Exon 11 of 11		NP_001356275.1
ASXL2	NM_001369347.1	c.1692delC	p.Ser565ValfsTer16	frameshift_variant	Exon 10 of 10		NP_001356276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASXL2	ENST00000435504.9	c.2472delC	p.Ser825ValfsTer16	frameshift_variant	Exon 13 of 13	5	NM_018263.6	ENSP00000391447.3
ASXL2	ENST00000336112.9	c.2469delC	p.Ser824ValfsTer16	frameshift_variant	Exon 12 of 12	1		ENSP00000337250.5
ASXL2	ENST00000404843.5	c.1692delC	p.Ser565ValfsTer45	frameshift_variant	Exon 9 of 10	1		ENSP00000383920.1
ASXL2	ENST00000673455.1	c.*113delC		downstream_gene_variant				ENSP00000500467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Shashi-Pena syndrome Pathogenic:1

Jan 25, 2018

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs886041068; hg19: chr2-25966733;