NM_018263.6:c.1143-27G>A

Variant names:

• chr2-25750440-C-T
• rs10178552
• NM_018263.6:c.1143-27G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018263.6(ASXL2):​c.1143-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,542,234 control chromosomes in the GnomAD database, including 79,039 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 0.32 (8432 hom., cov: 32)
  • Exomes 𝑓: 0.31 (70607 hom.)
• Consequence: ASXL2 NM_018263.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240
• Publications: 9 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018263.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASXL2	NM_018263.6	MANE Select	c.1143-27G>A		intron	N/A	NP_060733.4
	ASXL2	NM_001369346.1		c.969-27G>A		intron	N/A	NP_001356275.1
	ASXL2	NM_001369347.1		c.363-27G>A		intron	N/A	NP_001356276.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASXL2	ENST00000435504.9	TSL:5 MANE Select	c.1143-27G>A		intron	N/A	ENSP00000391447.3
	ASXL2	ENST00000336112.9	TSL:1	c.1140-27G>A		intron	N/A	ENSP00000337250.5
	ASXL2	ENST00000404843.5	TSL:1	c.363-27G>A		intron	N/A	ENSP00000383920.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48852 AN: 151880 Hom.: 8396 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.278 AC: 54129 AN: 194570 AF XY: 0.279

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.278

Gnomad EAS exome AF: 0.0911

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.313 AC: 434513 AN: 1390236 Hom.: 70607 Cov.: 27 AF XY: 0.311 AC XY: 213840 AN XY: 687780

African (AFR) AF: 0.419 AC: 12767 AN: 30462

American (AMR) AF: 0.193 AC: 5976 AN: 30924

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 5976 AN: 21860

East Asian (EAS) AF: 0.0668 AC: 2622 AN: 39252

South Asian (SAS) AF: 0.278 AC: 20644 AN: 74246

European-Finnish (FIN) AF: 0.225 AC: 11476 AN: 50966

Middle Eastern (MID) AF: 0.249 AC: 1353 AN: 5434

European-Non Finnish (NFE) AF: 0.330 AC: 356397 AN: 1079712

Other (OTH) AF: 0.302 AC: 17302 AN: 57380

GnomAD4 genome AF: 0.322 AC: 48957 AN: 151998 Hom.: 8432 Cov.: 32 AF XY: 0.315 AC XY: 23435 AN XY: 74308

African (AFR) AF: 0.413 AC: 17108 AN: 41416

American (AMR) AF: 0.257 AC: 3918 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 951 AN: 3472

East Asian (EAS) AF: 0.0863 AC: 447 AN: 5180

South Asian (SAS) AF: 0.275 AC: 1326 AN: 4814

European-Finnish (FIN) AF: 0.216 AC: 2287 AN: 10568

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21803 AN: 67956

Other (OTH) AF: 0.305 AC: 644 AN: 2114

Alfa AF: 0.311 Hom.: 2134

Bravo AF: 0.329

Asia WGS AF: 0.233 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.55
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10178552; hg19: chr2-25973309;