rs11631777

Positions:

• chr15-60392977-G-A
• chr15-60392977-G-T

Variant summary

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

The NM_004039.3(ANXA2):​c.-12+4966C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,201,658 control chromosomes in the GnomAD database, including 21,592 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 (2205 hom., cov: 31)
  • Exomes 𝑓: 0.19 (19387 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935

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]

ANXA2 (HGNC:):

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 (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.-12+4966C>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.-12+4966C>T		intron_variant		1	NM_004039.3	ENSP00000387545.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24776 AN: 151322 Hom.: 2207 Cov.: 31

Gnomad AFR AF: 0.112

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: 0.183

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.180

GnomAD4 exome AF: 0.189 AC: 198473 AN: 1050244 Hom.: 19387 AF XY: 0.190 AC XY: 97073 AN XY: 511236

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.221

Gnomad4 EAS exome AF: 0.0686

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.180

Gnomad4 NFE exome AF: 0.192

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.164 AC: 24772 AN: 151414 Hom.: 2205 Cov.: 31 AF XY: 0.163 AC XY: 12057 AN XY: 73900

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.0717

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.178

Alfa AF: 0.190 Hom.: 3812

Bravo AF: 0.160

Asia WGS AF: 0.122 AC: 425 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	0.27
DANN	Benign	0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11631777; hg19: chr15-60685176;