rs11553794

chr15-60364485-G-Achr15-60364485-G-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004039.3(ANXA2):c.187C>T(p.Arg63Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,613,150 control chromosomes in the GnomAD database, including 6 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 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00036 (6 hom.)
• Consequence: ANXA2 NM_004039.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.51

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019248098).
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA2	NM_004039.3	c.187C>T	p.Arg63Cys	missense_variant	4/13	ENST00000451270.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA2	ENST00000451270.7	c.187C>T	p.Arg63Cys	missense_variant	4/13	1	NM_004039.3	P1

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152130 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000747 AC: 187 AN: 250202 Hom.: 2 AF XY: 0.00108 AC XY: 146 AN XY: 135254

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000294

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00606

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000359 AC: 524 AN: 1460900 Hom.: 6 Cov.: 30 AF XY: 0.000542 AC XY: 394 AN XY: 726746

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.0000225

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00573

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000144

Gnomad4 OTH exome AF: 0.000199

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152250 Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 23 AN XY: 74434

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000127 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.000914 AC: 111

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Pathogenic	0.14
Cadd	Pathogenic	33
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.33	T;T;.;T;.;.;T;T;T;T;T;.;T;T;T;T;T;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.019	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-7.1	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0070	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;T
Sift4G	Uncertain	0.024	D;D;D;D;.;.;D;D;D;.;.;.;D;D;.;.;D;.
Polyphen		0.91	P;P;B;P;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Vest4		0.75
MutPred		0.79		Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);.;Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);.;Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);Loss of MoRF binding (P = 0.0444);
MVP		0.46
MPC		0.21
ClinPred		0.30	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.89
gMVP		0.86

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: rs11553794; hg19: chr15-60656684; COSMIC: COSV60317902;