rs17845226

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004039.3(ANXA2):c.292G>T(p.Val98Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,228 control chromosomes in the GnomAD database, including 12,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.086 ( 733 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11370 hom. )

Consequence

ANXA2
NM_004039.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002002865).

BP6

Variant 15-60361006-C-A is Benign according to our data. Variant chr15-60361006-C-A is described in ClinVar as [Benign]. Clinvar id is 1238049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA2	NM_004039.3 link	c.292G>T	p.Val98Leu	missense_variant	Exon 5 of 13	ENST00000451270.7	NP_004030.1	P07355-1A0A024R5Z7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7 link	c.292G>T	p.Val98Leu	missense_variant	Exon 5 of 13	1	NM_004039.3	ENSP00000387545.3		P07355-1

Frequencies

GnomAD3 genomes

AF:

0.0857

AC:

13041

AN:

152148

Hom.:

733

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0227

Gnomad AMI

AF:

0.0461

Gnomad AMR

AF:

0.0797

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0481

Gnomad FIN

AF:

0.100

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.0855

GnomAD3 exomes

AF:

0.0919

AC:

23107

AN:

251394

Hom.:

1405

AF XY:

0.0948

AC XY:

12875

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.0208

Gnomad AMR exome

AF:

0.0555

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0488

Gnomad FIN exome

AF:

0.0944

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.119

AC:

173316

AN:

1460962

Hom.:

11370

Cov.:

AF XY:

0.117

AC XY:

84766

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.0577

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0515

Gnomad4 FIN exome

AF:

0.0967

Gnomad4 NFE exome

AF:

0.135

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0856

AC:

13036

AN:

152266

Hom.:

733

Cov.:

AF XY:

0.0827

AC XY:

6156

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.0796

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.0487

Gnomad4 FIN

AF:

0.100

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.0846

Alfa

AF:

0.113

Hom.:

514

Bravo

AF:

0.0818

TwinsUK

AF:

0.134

AC:

497

ALSPAC

AF:

0.126

AC:

485

ESP6500AA

AF:

0.0238

AC:

105

ESP6500EA

AF:

0.133

AC:

1144

ExAC

AF:

0.0936

AC:

11367

Asia WGS

AF:

0.0240

AC:

AN:

3478

EpiCase

AF:

0.134

EpiControl

AF:

0.138

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 23, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28456096) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

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

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.053

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.94

.;.;D;D;D;D;D;.;.;D;D;D;D;.;D;D;D

MetaRNN

Benign

0.0020

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

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.62

N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.33

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

Sift4G

Benign

0.73

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

Polyphen

0.0

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

Vest4

0.15

MutPred

0.24

Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);.;Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);.;Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);Gain of disorder (P = 0.0627);.;Gain of disorder (P = 0.0627);

MPC

0.13

ClinPred

0.0081

GERP RS

5.4

Varity_R

0.21

gMVP

0.49

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