Variant 15-60382402-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000451270.7(ANXA2):c.88T>C(p.Tyr30His) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ANXA2
ENST00000451270.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17700168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA2	NM_004039.3 linkuse as main transcript	c.88T>C	p.Tyr30His	missense_variant	3/13	ENST00000451270.7	NP_004030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7 linkuse as main transcript	c.88T>C	p.Tyr30His	missense_variant	3/13	1	NM_004039.3	ENSP00000387545	P1	P07355-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727144

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.142T>C (p.Y48H) alteration is located in exon 3 (coding exon 3) of the ANXA2 gene. This alteration results from a T to C substitution at nucleotide position 142, causing the tyrosine (Y) at amino acid position 48 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

0.00061

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T;.;T;.;.;T;T;T;T;T;.;T;T;T;T;T;.;.

Eigen

Benign

-0.24

Eigen_PC

Benign

0.0073

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.74

.;.;T;T;T;T;.;.;T;T;T;T;.;T;T;T;T;D;D

M_CAP

Benign

0.0085

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

0.95

D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.9

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;D

REVEL

Benign

0.11

Sift

Benign

0.38

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;D

Sift4G

Benign

0.47

T;T;T;T;.;.;T;T;T;.;.;.;T;T;.;.;T;.;.

Polyphen

0.0020

B;B;B;B;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

Vest4

0.58

MutPred

0.38

Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);.;Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);.;Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);Loss of phosphorylation at Y30 (P = 0.0231);

MVP

0.28

MPC

0.19

ClinPred

0.49

GERP RS

5.7

Varity_R

0.31

gMVP

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over