rs11633657

Positions:

• chr15-60351958-C-T

Variant summary

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

The NM_004039.3(ANXA2):​c.683-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 659,446 control chromosomes in the GnomAD database, including 30,013 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 0.27 (6195 hom., cov: 31)
  • Exomes 𝑓: 0.30 (23818 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

Genes affected

ANXA2 (HGNC:537): (annexin A2) This gene encodes a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cellular growth and in signal transduction pathways. This protein functions as an autocrine factor which heightens osteoclast formation and bone resorption. This gene has three pseudogenes located on chromosomes 4, 9 and 10, respectively. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. Annexin A2 expression has been found to correlate with resistance to treatment against various cancer forms. [provided by RefSeq, Dec 2019]

ANXA2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA2	NM_004039.3	c.683-139G>A		intron_variant		ENST00000451270.7	NP_004030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7	c.683-139G>A		intron_variant		1	NM_004039.3	ENSP00000387545.3

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41363 AN: 151922 Hom.: 6194 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.296 AC: 150157 AN: 507406 Hom.: 23818 AF XY: 0.296 AC XY: 79118 AN XY: 267480

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.244

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.328

Gnomad4 OTH exome AF: 0.302

GnomAD4 genome AF: 0.272 AC: 41368 AN: 152040 Hom.: 6195 Cov.: 31 AF XY: 0.269 AC XY: 20009 AN XY: 74320

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.291

Alfa AF: 0.278 Hom.: 1193

Bravo AF: 0.268

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.69
DANN	Benign	0.48

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: rs11633657; hg19: chr15-60644157;