Genetic Variant ASXL2:p.Pro808dup (chr2-25743912-T-TGGG) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting

The NM_018263.6(ASXL2):c.2422_2424dupCCC(p.Pro808dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ASXL2
NM_018263.6 conservative_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.490

Variant links:

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]

ASXL2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_018263.6. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASXL2	NM_018263.6 link	c.2422_2424dupCCC	p.Pro808dup	conservative_inframe_insertion	Exon 13 of 13	ENST00000435504.9	NP_060733.4	Q76L83-1
ASXL2	NM_001369346.1 link	c.2248_2250dupCCC	p.Pro750dup	conservative_inframe_insertion	Exon 11 of 11		NP_001356275.1
ASXL2	NM_001369347.1 link	c.1642_1644dupCCC	p.Pro548dup	conservative_inframe_insertion	Exon 10 of 10		NP_001356276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASXL2	ENST00000435504.9 link	c.2422_2424dupCCC	p.Pro808dup	conservative_inframe_insertion	Exon 13 of 13	5	NM_018263.6	ENSP00000391447.3	Q76L83-1
ASXL2	ENST00000336112.9 link	c.2419_2421dupCCC	p.Pro807dup	conservative_inframe_insertion	Exon 12 of 12	1		ENSP00000337250.5	E7EWD6
ASXL2	ENST00000404843.5 link	c.1642_1644dupCCC	p.Pro548dup	conservative_inframe_insertion	Exon 9 of 10	1		ENSP00000383920.1	Q76L83-2
ASXL2	ENST00000673455.1 link	c.63_65dupCCC		downstream_gene_variant				ENSP00000500467.1	A0A5F9ZHN2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

No publications associated with this variant yet.

2-25743912-TG-TGGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over