Genetic Variant NM_004039.3:c.778+70G>C (chr15-60351654-C-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.778+70G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 974,258 control chromosomes in the GnomAD database, including 283,955 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 0.79 ( 47869 hom., cov: 31)

Exomes 𝑓: 0.75 ( 236086 hom. )

Consequence

ANXA2
NM_004039.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANXA2	NM_004039.3 link	c.778+70G>C		intron_variant	Intron 10 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.778+70G>C		intron_variant	Intron 10 of 12	1	NM_004039.3	ENSP00000387545.3		P07355-1

Frequencies

GnomAD3 genomes

AF:

0.790

AC:

120007

AN:

151980

Hom.:

47805

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.759

Gnomad AMR

AF:

0.850

Gnomad ASJ

AF:

0.774

Gnomad EAS

AF:

0.603

Gnomad SAS

AF:

0.703

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.762

Gnomad OTH

AF:

0.788

GnomAD4 exome

AF:

0.755

AC:

620401

AN:

822160

Hom.:

236086

Cov.:

AF XY:

0.751

AC XY:

325554

AN XY:

433234

show subpopulations

African (AFR)

AF:

0.880

AC:

18448

AN:

20952

American (AMR)

AF:

0.891

AC:

37778

AN:

42376

Ashkenazi Jewish (ASJ)

AF:

0.772

AC:

16310

AN:

21132

East Asian (EAS)

AF:

0.559

AC:

20552

AN:

36798

South Asian (SAS)

AF:

0.710

AC:

50071

AN:

70558

European-Finnish (FIN)

AF:

0.698

AC:

36711

AN:

52564

Middle Eastern (MID)

AF:

0.773

AC:

3338

AN:

4316

European-Non Finnish (NFE)

AF:

0.762

AC:

407168

AN:

534350

Other (OTH)

AF:

0.768

AC:

30025

AN:

39114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7807

15614

23421

31228

39035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6050

12100

18150

24200

30250

<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:

0.790

AC:

120137

AN:

152098

Hom.:

47869

Cov.:

AF XY:

0.786

AC XY:

58423

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.875

AC:

36300

AN:

41492

American (AMR)

AF:

0.851

AC:

13010

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.774

AC:

2687

AN:

3472

East Asian (EAS)

AF:

0.603

AC:

3113

AN:

5162

South Asian (SAS)

AF:

0.704

AC:

3395

AN:

4822

European-Finnish (FIN)

AF:

0.686

AC:

7240

AN:

10558

Middle Eastern (MID)

AF:

0.772

AC:

227

AN:

294

European-Non Finnish (NFE)

AF:

0.762

AC:

51805

AN:

67978

Other (OTH)

AF:

0.789

AC:

1668

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1299

2598

3897

5196

6495

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<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:

0.653

Hom.:

1284

Bravo

AF:

0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.057

(source)

DANN

Benign

0.41

PhyloP100

-1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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