rs7183894

Positions:

• chr15-60383031-A-G

Variant summary

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

The NM_004039.3(ANXA2):​c.49-590T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,550 control chromosomes in the GnomAD database, including 49,269 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 0.80 (49120 hom., cov: 31)
  • Exomes 𝑓: 0.83 (149 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA2	NM_004039.3	c.49-590T>C		intron_variant		ENST00000451270.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA2	ENST00000451270.7	c.49-590T>C		intron_variant		1	NM_004039.3	P1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121533 AN: 152000 Hom.: 49095 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.804

GnomAD4 exome AF: 0.831 AC: 359 AN: 432 Hom.: 149 Cov.: 0 AF XY: 0.821 AC XY: 220 AN XY: 268

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.909

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.821

Gnomad4 NFE exome AF: 0.831

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.799 AC: 121608 AN: 152118 Hom.: 49120 Cov.: 31 AF XY: 0.806 AC XY: 59913 AN XY: 74366

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.800

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.868

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.807

Alfa AF: 0.812 Hom.: 12521

Bravo AF: 0.792

Asia WGS AF: 0.950 AC: 3304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.29

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: rs7183894; hg19: chr15-60675230;