Variant 20-32358788-CAGA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3BP6_Very_StrongBS2_Supporting

The NM_015338.6(ASXL1):c.25_27del(p.Lys9del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,460,560 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

ASXL1
NM_015338.6 inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

ASXL1 (HGNC:18318): (ASXL transcriptional regulator 1) This gene is similar to the Drosophila additional sex combs gene, which encodes a chromatin-binding protein required for normal determination of segment identity in the developing embryo. The protein is a member of the Polycomb group of proteins, which are necessary for the maintenance of stable repression of homeotic and other loci. The protein is thought to disrupt chromatin in localized areas, enhancing transcription of certain genes while repressing the transcription of other genes. The protein encoded by this gene functions as a ligand-dependent co-activator for retinoic acid receptor in cooperation with nuclear receptor coactivator 1. Mutations in this gene are associated with myelodysplastic syndromes and chronic myelomonocytic leukemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

ASXL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_015338.6

BP6

Variant 20-32358788-CAGA-C is Benign according to our data. Variant chr20-32358788-CAGA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1272899.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 10 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ASXL1	NM_015338.6 linkuse as main transcript	c.25_27del	p.Lys9del	inframe_deletion	1/13	ENST00000375687.10
ASXL1	NM_001164603.1 linkuse as main transcript	c.25_27del	p.Lys9del	inframe_deletion	1/5
ASXL1	XM_006723727.4 linkuse as main transcript	c.25_27del	p.Lys9del	inframe_deletion	1/12
ASXL1	XM_047439945.1 linkuse as main transcript	c.25_27del	p.Lys9del	inframe_deletion	1/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASXL1	ENST00000375687.10 linkuse as main transcript	c.25_27del	p.Lys9del	inframe_deletion	1/13	5	NM_015338.6	P1	Q8IXJ9-1

Frequencies

GnomAD3 genomes

AF:

0.0000665

AC:

AN:

150372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000997

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000889

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000418

AC:

AN:

112320

Hom.:

AF XY:

0.000453

AC XY:

AN XY:

61800

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.000139

Gnomad EAS exome

AF:

0.00155

Gnomad SAS exome

AF:

0.000519

Gnomad FIN exome

AF:

0.000133

Gnomad NFE exome

AF:

0.000525

Gnomad OTH exome

AF:

0.000317

GnomAD4 exome

AF:

0.000192

AC:

252

AN:

1310082

Hom.:

AF XY:

0.000194

AC XY:

125

AN XY:

645518

show subpopulations

Gnomad4 AFR exome

AF:

0.000267

Gnomad4 AMR exome

AF:

0.000292

Gnomad4 ASJ exome

AF:

0.0000902

Gnomad4 EAS exome

AF:

0.000851

Gnomad4 SAS exome

AF:

0.000226

Gnomad4 FIN exome

AF:

0.000147

Gnomad4 NFE exome

AF:

0.000174

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.0000665

AC:

AN:

150478

Hom.:

Cov.:

AF XY:

0.0000680

AC XY:

AN XY:

73566

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.0000661

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000997

Gnomad4 NFE

AF:

0.0000889

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	ASXL1: BP3 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 23, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over