rs17680828

Positions:

• chr2-25767771-T-C

Variant summary

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

The NM_018263.6(ASXL2):​c.632-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,598,202 control chromosomes in the GnomAD database, including 33,819 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 0.15 (2174 hom., cov: 33)
  • Exomes 𝑓: 0.20 (31645 hom.)
• Consequence: ASXL2 NM_018263.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

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=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASXL2	NM_018263.6	c.632-45A>G		intron_variant		ENST00000435504.9	NP_060733.4
ASXL2	NM_001369346.1	c.458-45A>G		intron_variant			NP_001356275.1
ASXL2	NM_001369347.1	c.-149-45A>G		intron_variant			NP_001356276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASXL2	ENST00000435504.9	c.632-45A>G		intron_variant		5	NM_018263.6	ENSP00000391447	P4
ASXL2	ENST00000336112.9	c.629-45A>G		intron_variant		1		ENSP00000337250	A2
ASXL2	ENST00000404843.5	c.-149-45A>G		intron_variant		1		ENSP00000383920	A2
ASXL2	ENST00000673455.1	c.-149-45A>G		intron_variant				ENSP00000500467

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22989 AN: 152166 Hom.: 2166 Cov.: 33

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.148

GnomAD3 exomes AF: 0.166 AC: 40550 AN: 244364 Hom.: 3786 AF XY: 0.168 AC XY: 22338 AN XY: 132626

Gnomad AFR exome AF: 0.0434

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.0899

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.169

Gnomad NFE exome AF: 0.213

Gnomad OTH exome AF: 0.182

GnomAD4 exome AF: 0.203 AC: 293550 AN: 1445916 Hom.: 31645 Cov.: 27 AF XY: 0.201 AC XY: 144936 AN XY: 719358

Gnomad4 AFR exome AF: 0.0393

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.0664

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.171

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.151 AC: 23021 AN: 152286 Hom.: 2174 Cov.: 33 AF XY: 0.148 AC XY: 11039 AN XY: 74476

Gnomad4 AFR AF: 0.0478

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0861

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.157

Alfa AF: 0.177 Hom.: 608

Bravo AF: 0.145

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.4
DANN	Benign	0.80

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: rs17680828; hg19: chr2-25990640; COSMIC: COSV55458403; COSMIC: COSV55458403;