dbSNP rs62004988: ANXA2:c.-11-5324C>T (chr15-60391410-G-A) – 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.-11-5324C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,304 control chromosomes in the GnomAD database, including 2,184 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 0.16 ( 2183 hom., cov: 32)

Exomes 𝑓: 0.12 ( 1 hom. )

Consequence

ANXA2
NM_004039.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.51

Publications

1 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:

Genome browser will be placed here

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=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA2	NM_004039.3 link	c.-11-5324C>T		intron_variant	Intron 1 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.-11-5324C>T		intron_variant	Intron 1 of 12	1	NM_004039.3	ENSP00000387545.3		P07355-1

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24585

AN:

152046

Hom.:

2185

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.0712

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.192

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.121

AC:

AN:

140

Hom.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.107

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.162

AC:

24585

AN:

152164

Hom.:

2183

Cov.:

AF XY:

0.162

AC XY:

12036

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.103

AC:

4291

AN:

41520

American (AMR)

AF:

0.161

AC:

2461

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

775

AN:

3472

East Asian (EAS)

AF:

0.0718

AC:

372

AN:

5184

South Asian (SAS)

AF:

0.191

AC:

921

AN:

4826

European-Finnish (FIN)

AF:

0.189

AC:

1997

AN:

10594

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.192

AC:

13023

AN:

67982

Other (OTH)

AF:

0.175

AC:

368

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1046

2092

3137

4183

5229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.159

Hom.:

259

Bravo

AF:

0.158

Asia WGS

AF:

0.120

AC:

415

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.023

(source)

DANN

Benign

0.57

PhyloP100

-2.5

PromoterAI

0.048

Neutral

(source)

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