dbSNP rs7183894: ANXA2:c.49-590T>C (chr15-60383031-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004039.3(ANXA2):c.49-590T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,550 control chromosomes in the GnomAD database, including 49,269 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 0.80 ( 49120 hom., cov: 31)

Exomes 𝑓: 0.83 ( 149 hom. )

Consequence

ANXA2
NM_004039.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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 rank	MANE	Protein	UniProt
ANXA2	NM_004039.3 link	c.49-590T>C		intron_variant	Intron 2 of 12	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.49-590T>C		intron_variant	Intron 2 of 12	1	NM_004039.3	ENSP00000387545.3		P07355-1

Frequencies

GnomAD3 genomes

AF:

0.800

AC:

121533

AN:

152000

Hom.:

49095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.927

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.800

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.948

Gnomad FIN

AF:

0.868

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.825

Gnomad OTH

AF:

0.804

GnomAD4 exome

AF:

0.831

AC:

359

AN:

432

Hom.:

149

Cov.:

AF XY:

0.821

AC XY:

220

AN XY:

268

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.909

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.821

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.831

AC:

281

AN:

338

Other (OTH)

AF:

0.650

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.799

AC:

121608

AN:

152118

Hom.:

49120

Cov.:

AF XY:

0.806

AC XY:

59913

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.681

AC:

28220

AN:

41442

American (AMR)

AF:

0.837

AC:

12805

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.800

AC:

2777

AN:

3470

East Asian (EAS)

AF:

0.999

AC:

5174

AN:

5180

South Asian (SAS)

AF:

0.947

AC:

4561

AN:

4816

European-Finnish (FIN)

AF:

0.868

AC:

9202

AN:

10602

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.825

AC:

56095

AN:

67998

Other (OTH)

AF:

0.807

AC:

1701

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1205

2411

3616

4822

6027

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

876

1752

2628

3504

4380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.809

Hom.:

12690

Bravo

AF:

0.792

Asia WGS

AF:

0.950

AC:

3304

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.30

(source)

DANN

Benign

0.29

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over