15-60380752-T-C

Variant names:

• chr15-60380752-T-C
• rs12909425
• NM_004039.3:c.148+1590A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004039.3(ANXA2):​c.148+1590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.62 (27850 hom., cov: 19)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004039.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA2	NM_004039.3	MANE Select	c.148+1590A>G		intron	N/A	NP_004030.1	P07355-1
	ANXA2	NM_001002858.3		c.202+1590A>G		intron	N/A	NP_001002858.1	P07355-2
	ANXA2	NM_001002857.2		c.148+1590A>G		intron	N/A	NP_001002857.1	P07355-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA2	ENST00000451270.7	TSL:1 MANE Select	c.148+1590A>G		intron	N/A	ENSP00000387545.3	P07355-1
	ANXA2	ENST00000332680.8	TSL:1	c.202+1590A>G		intron	N/A	ENSP00000346032.3	P07355-2
	ANXA2	ENST00000396024.7	TSL:1	c.148+1590A>G		intron	N/A	ENSP00000379342.3	P07355-1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 88144 AN: 142346 Hom.: 27829 Cov.: 19

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.634

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.619 AC: 88199 AN: 142416 Hom.: 27850 Cov.: 19 AF XY: 0.623 AC XY: 42642 AN XY: 68500

African (AFR) AF: 0.775 AC: 29515 AN: 38092

American (AMR) AF: 0.604 AC: 8343 AN: 13804

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2107 AN: 3442

East Asian (EAS) AF: 0.438 AC: 2087 AN: 4764

South Asian (SAS) AF: 0.610 AC: 2724 AN: 4468

European-Finnish (FIN) AF: 0.582 AC: 4798 AN: 8242

Middle Eastern (MID) AF: 0.719 AC: 200 AN: 278

European-Non Finnish (NFE) AF: 0.552 AC: 36696 AN: 66476

Other (OTH) AF: 0.629 AC: 1227 AN: 1950

Alfa AF: 0.414 Hom.: 1024

Bravo AF: 0.622

Asia WGS AF: 0.528 AC: 1839 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.49
PhyloP100		-3.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12909425; hg19: chr15-60672951;