Genetic Variant NM_004039.3:c.683-139G>A (chr15-60351958-C-T) – 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.683-139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 659,446 control chromosomes in the GnomAD database, including 30,013 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 0.27 ( 6195 hom., cov: 31)

Exomes 𝑓: 0.30 ( 23818 hom. )

Consequence

ANXA2
NM_004039.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.597

Publications

10 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA2	NM_004039.3 link	c.683-139G>A		intron_variant	Intron 9 of 12	ENST00000451270.7	NP_004030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7 link	c.683-139G>A		intron_variant	Intron 9 of 12	1	NM_004039.3	ENSP00000387545.3

Frequencies

GnomAD3 genomes

AF:

0.272

AC:

41363

AN:

151922

Hom.:

6194

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.367

Gnomad EAS

AF:

0.105

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.275

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.333

Gnomad OTH

AF:

0.292

GnomAD4 exome

AF:

0.296

AC:

150157

AN:

507406

Hom.:

23818

AF XY:

0.296

AC XY:

79118

AN XY:

267480

show subpopulations

African (AFR)

AF:

0.198

AC:

2657

AN:

13424

American (AMR)

AF:

0.222

AC:

4577

AN:

20624

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

5284

AN:

14364

East Asian (EAS)

AF:

0.108

AC:

3398

AN:

31500

South Asian (SAS)

AF:

0.244

AC:

11500

AN:

47090

European-Finnish (FIN)

AF:

0.287

AC:

11863

AN:

41290

Middle Eastern (MID)

AF:

0.405

AC:

1493

AN:

3688

European-Non Finnish (NFE)

AF:

0.328

AC:

100962

AN:

307520

Other (OTH)

AF:

0.302

AC:

8423

AN:

27906

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

5052

10104

15157

20209

25261

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.272

AC:

41368

AN:

152040

Hom.:

6195

Cov.:

AF XY:

0.269

AC XY:

20009

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.195

AC:

8092

AN:

41490

American (AMR)

AF:

0.251

AC:

3838

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.367

AC:

1269

AN:

3462

East Asian (EAS)

AF:

0.106

AC:

547

AN:

5182

South Asian (SAS)

AF:

0.230

AC:

1110

AN:

4818

European-Finnish (FIN)

AF:

0.275

AC:

2901

AN:

10548

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.333

AC:

22654

AN:

67948

Other (OTH)

AF:

0.291

AC:

613

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1491

2982

4472

5963

7454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<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:

0.275

Hom.:

1208

Bravo

AF:

0.268

Asia WGS

AF:

0.158

AC:

550

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.69

(source)

DANN

Benign

0.48

PhyloP100

-0.60

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