15-60383031-A-G

Variant names:

• chr15-60383031-A-G
• rs7183894
• NM_004039.3:c.49-590T>C

Variant summary

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

The NM_004039.3(ANXA2):​c.49-590T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,550 control chromosomes in the GnomAD database, including 49,269 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 0.80 (49120 hom., cov: 31)
  • Exomes 𝑓: 0.83 (149 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA2	NM_004039.3	MANE Select	c.49-590T>C		intron	N/A	NP_004030.1
	ANXA2	NM_001002858.3		c.103-590T>C		intron	N/A	NP_001002858.1
	ANXA2	NM_001002857.2		c.49-590T>C		intron	N/A	NP_001002857.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA2	ENST00000451270.7	TSL:1 MANE Select	c.49-590T>C		intron	N/A	ENSP00000387545.3
	ANXA2	ENST00000332680.8	TSL:1	c.103-590T>C		intron	N/A	ENSP00000346032.3
	ANXA2	ENST00000396024.7	TSL:1	c.49-590T>C		intron	N/A	ENSP00000379342.3

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121533 AN: 152000 Hom.: 49095 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.868

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.804

GnomAD4 exome AF: 0.831 AC: 359 AN: 432 Hom.: 149 Cov.: 0 AF XY: 0.821 AC XY: 220 AN XY: 268

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.909 AC: 20 AN: 22

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AF: 1.00 AC: 10 AN: 10

European-Finnish (FIN) AF: 0.821 AC: 23 AN: 28

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.831 AC: 281 AN: 338

Other (OTH) AF: 0.650 AC: 13 AN: 20

GnomAD4 genome AF: 0.799 AC: 121608 AN: 152118 Hom.: 49120 Cov.: 31 AF XY: 0.806 AC XY: 59913 AN XY: 74366

African (AFR) AF: 0.681 AC: 28220 AN: 41442

American (AMR) AF: 0.837 AC: 12805 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2777 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5174 AN: 5180

South Asian (SAS) AF: 0.947 AC: 4561 AN: 4816

European-Finnish (FIN) AF: 0.868 AC: 9202 AN: 10602

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56095 AN: 67998

Other (OTH) AF: 0.807 AC: 1701 AN: 2108

Alfa AF: 0.809 Hom.: 12690

Bravo AF: 0.792

Asia WGS AF: 0.950 AC: 3304 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.29
PhyloP100		-1.1
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: rs7183894; hg19: chr15-60675230;