rs11633619

Variant names:

• chr15-60351875-C-T
• rs11633619
• NM_004039.3:c.683-56G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004039.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA2	NM_004039.3	MANE Select	c.683-56G>A		intron	N/A	NP_004030.1
	ANXA2	NM_001002858.3		c.737-56G>A		intron	N/A	NP_001002858.1
	ANXA2	NM_001002857.2		c.683-56G>A		intron	N/A	NP_001002857.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA2	ENST00000451270.7	TSL:1 MANE Select	c.683-56G>A		intron	N/A	ENSP00000387545.3
	ANXA2	ENST00000332680.8	TSL:1	c.737-56G>A		intron	N/A	ENSP00000346032.3
	ANXA2	ENST00000396024.7	TSL:1	c.683-56G>A		intron	N/A	ENSP00000379342.3

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

African (AFR) AF: 0.195 AC: 4853 AN: 24868

American (AMR) AF: 0.192 AC: 7826 AN: 40708

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 8475 AN: 23106

East Asian (EAS) AF: 0.109 AC: 4096 AN: 37662

South Asian (SAS) AF: 0.247 AC: 18589 AN: 75328

European-Finnish (FIN) AF: 0.286 AC: 15167 AN: 52944

Middle Eastern (MID) AF: 0.402 AC: 1985 AN: 4940

European-Non Finnish (NFE) AF: 0.340 AC: 255242 AN: 751776

Other (OTH) AF: 0.308 AC: 14397 AN: 46726

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

African (AFR) AF: 0.196 AC: 8135 AN: 41492

American (AMR) AF: 0.252 AC: 3846 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3468

East Asian (EAS) AF: 0.105 AC: 546 AN: 5176

South Asian (SAS) AF: 0.231 AC: 1112 AN: 4818

European-Finnish (FIN) AF: 0.275 AC: 2909 AN: 10580

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22663 AN: 67972

Other (OTH) AF: 0.291 AC: 613 AN: 2110

Alfa AF: 0.311 Hom.: 26145

Bravo AF: 0.268

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.66
PhyloP100		-0.20
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: rs11633619; hg19: chr15-60644074; COSMIC: COSV60315996; COSMIC: COSV60315996;