rs62004988

Positions:

• chr15-60391410-G-A

Variant summary

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

The NM_004039.3(ANXA2):​c.-11-5324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,304 control chromosomes in the GnomAD database, including 2,184 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 0.16 (2183 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA2	NM_004039.3	c.-11-5324C>T		intron_variant		ENST00000451270.7	NP_004030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7	c.-11-5324C>T		intron_variant		1	NM_004039.3	ENSP00000387545	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24585 AN: 152046 Hom.: 2185 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0712

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.121 AC: 17 AN: 140 Hom.: 1 AF XY: 0.143 AC XY: 12 AN XY: 84

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.0714

GnomAD4 genome AF: 0.162 AC: 24585 AN: 152164 Hom.: 2183 Cov.: 32 AF XY: 0.162 AC XY: 12036 AN XY: 74392

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0718

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.175

Alfa AF: 0.162 Hom.: 258

Bravo AF: 0.158

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.023
DANN	Benign	0.57

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: rs62004988; hg19: chr15-60683609;