rs6546452

Positions:

• chr2-25758403-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018263.6(ASXL2):​c.939+1079C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,058 control chromosomes in the GnomAD database, including 2,532 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2532 hom., cov: 31)
• Consequence: ASXL2 NM_018263.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASXL2	NM_018263.6	c.939+1079C>T		intron_variant		ENST00000435504.9	NP_060733.4
ASXL2	NM_001369346.1	c.765+1079C>T		intron_variant			NP_001356275.1
ASXL2	NM_001369347.1	c.159+1079C>T		intron_variant			NP_001356276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASXL2	ENST00000435504.9	c.939+1079C>T		intron_variant		5	NM_018263.6	ENSP00000391447	P4
ASXL2	ENST00000336112.9	c.936+1079C>T		intron_variant		1		ENSP00000337250	A2
ASXL2	ENST00000404843.5	c.159+1079C>T		intron_variant		1		ENSP00000383920	A2
ASXL2	ENST00000673455.1	c.159+1079C>T		intron_variant				ENSP00000500467

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26514 AN: 151938 Hom.: 2520 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0860

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.175 AC: 26568 AN: 152058 Hom.: 2532 Cov.: 31 AF XY: 0.172 AC XY: 12769 AN XY: 74356

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0860

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.175

Alfa AF: 0.205 Hom.: 6113

Bravo AF: 0.174

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.13

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: rs6546452; hg19: chr2-25981272;