15-60386151-T-C

Variant summary

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

The NM_004039.3(ANXA2):c.-11-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,146,192 control chromosomes in the GnomAD database, including 392,106 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 (47888 hom., cov: 33)
  • Exomes 𝑓: 0.83 (344218 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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=-0.82).
• 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.-11-65A>G		intron_variant		ENST00000451270.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA2	ENST00000451270.7	c.-11-65A>G		intron_variant		1	NM_004039.3	P1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119656 AN: 152022 Hom.: 47862 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.795

GnomAD4 exome AF: 0.830 AC: 825044 AN: 994052 Hom.: 344218 Cov.: 13 AF XY: 0.834 AC XY: 427417 AN XY: 512586

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.870

Gnomad4 ASJ exome AF: 0.817

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.862

Gnomad4 NFE exome AF: 0.815

Gnomad4 OTH exome AF: 0.817

GnomAD4 genome AF: 0.787 AC: 119728 AN: 152140 Hom.: 47888 Cov.: 33 AF XY: 0.794 AC XY: 59057 AN XY: 74394

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.797

Alfa AF: 0.821 Hom.: 22479

Bravo AF: 0.778

Asia WGS AF: 0.943 AC: 3278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.62

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: rs7182242; hg19: chr15-60678350;