rs8037326

Positions:

• chr15-60351654-C-G
• chr15-60351654-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.778+70G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 974,258 control chromosomes in the GnomAD database, including 283,955 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 0.79 (47869 hom., cov: 31)
  • Exomes 𝑓: 0.75 (236086 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA2	NM_004039.3	c.778+70G>C		intron_variant		ENST00000451270.7	NP_004030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7	c.778+70G>C		intron_variant		1	NM_004039.3	ENSP00000387545.3

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120007 AN: 151980 Hom.: 47805 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.755 AC: 620401 AN: 822160 Hom.: 236086 Cov.: 11 AF XY: 0.751 AC XY: 325554 AN XY: 433234

Gnomad4 AFR exome AF: 0.880

Gnomad4 AMR exome AF: 0.891

Gnomad4 ASJ exome AF: 0.772

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.698

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.768

GnomAD4 genome AF: 0.790 AC: 120137 AN: 152098 Hom.: 47869 Cov.: 31 AF XY: 0.786 AC XY: 58423 AN XY: 74370

Gnomad4 AFR AF: 0.875

Gnomad4 AMR AF: 0.851

Gnomad4 ASJ AF: 0.774

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.686

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.789

Alfa AF: 0.653 Hom.: 1284

Bravo AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
DANN	Benign	0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8037326; hg19: chr15-60643853; COSMIC: COSV60315534; COSMIC: COSV60315534;