rs11633619

Positions:

• chr15-60351875-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.683-56G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,210,164 control chromosomes in the GnomAD database, including 59,358 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 (6207 hom., cov: 32)
  • Exomes 𝑓: 0.31 (53151 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204

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]

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	UniProt
ANXA2	NM_004039.3	c.683-56G>A		intron_variant		ENST00000451270.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA2	ENST00000451270.7	c.683-56G>A		intron_variant		1	NM_004039.3	P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41436 AN: 151988 Hom.: 6206 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.292

GnomAD4 exome AF: 0.312 AC: 330630 AN: 1058058 Hom.: 53151 AF XY: 0.312 AC XY: 169768 AN XY: 543658

Gnomad4 AFR exome AF: 0.195

Gnomad4 AMR exome AF: 0.192

Gnomad4 ASJ exome AF: 0.367

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.247

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.308

GnomAD4 genome AF: 0.272 AC: 41441 AN: 152106 Hom.: 6207 Cov.: 32 AF XY: 0.270 AC XY: 20060 AN XY: 74368

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.367

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.275

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.291

Alfa AF: 0.322 Hom.: 10401

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	1.2
DANN	Benign	0.66

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: rs11633619; hg19: chr15-60644074; COSMIC: COSV60315996; COSMIC: COSV60315996;