NM_004039.3:c.148+1590A>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004039.3(ANXA2):​c.148+1590A>C 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 0.0000070 (0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A	NP_004030.1	P07355-1
	ANXA2	NM_001002858.3		c.202+1590A>C		intron	N/A	NP_001002858.1	P07355-2
	ANXA2	NM_001002857.2		c.148+1590A>C		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>C		intron	N/A	ENSP00000387545.3	P07355-1
	ANXA2	ENST00000332680.8	TSL:1	c.202+1590A>C		intron	N/A	ENSP00000346032.3	P07355-2
	ANXA2	ENST00000396024.7	TSL:1	c.148+1590A>C		intron	N/A	ENSP00000379342.3	P07355-1

Frequencies

GnomAD3 genomes AF: 0.00000702 AC: 1 AN: 142550 Hom.: 0 Cov.: 19

Gnomad AFR AF: 0.0000263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000702 AC: 1 AN: 142550 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 68516

African (AFR) AF: 0.0000263 AC: 1 AN: 38044

American (AMR) AF: 0.00 AC: 0 AN: 13814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 4784

South Asian (SAS) AF: 0.00 AC: 0 AN: 4490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66570

Other (OTH) AF: 0.00 AC: 0 AN: 1936

Alfa AF: 0.00 Hom.: 1024

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.46
DANN	Benign	0.47
PhyloP100		-3.5

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;