rs6546452

Variant names:

• chr2-25758403-G-A
• rs6546452
• NM_018263.6:c.939+1079C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Shashi-Pena syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ASXL2	NM_018263.6	c.939+1079C>T		intron_variant	Intron 9 of 12	ENST00000435504.9	NP_060733.4
ASXL2	NM_001369346.1	c.765+1079C>T		intron_variant	Intron 7 of 10		NP_001356275.1
ASXL2	NM_001369347.1	c.159+1079C>T		intron_variant	Intron 6 of 9		NP_001356276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASXL2	ENST00000435504.9	c.939+1079C>T		intron_variant	Intron 9 of 12	5	NM_018263.6	ENSP00000391447.3
ASXL2	ENST00000336112.9	c.936+1079C>T		intron_variant	Intron 8 of 11	1		ENSP00000337250.5
ASXL2	ENST00000404843.5	c.159+1079C>T		intron_variant	Intron 5 of 9	1		ENSP00000383920.1
ASXL2	ENST00000673455.1	c.159+1079C>T		intron_variant	Intron 6 of 9			ENSP00000500467.1

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

African (AFR) AF: 0.126 AC: 5215 AN: 41502

American (AMR) AF: 0.164 AC: 2506 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3468

East Asian (EAS) AF: 0.0860 AC: 445 AN: 5174

South Asian (SAS) AF: 0.165 AC: 797 AN: 4820

European-Finnish (FIN) AF: 0.163 AC: 1717 AN: 10556

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14788 AN: 67950

Other (OTH) AF: 0.175 AC: 370 AN: 2110

Alfa AF: 0.201 Hom.: 12383

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
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6546452; hg19: chr2-25981272;