15-60386151-T-C

Variant names:

• chr15-60386151-T-C
• rs7182242
• NM_004039.3:c.-11-65A>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.-11-65A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,146,192 control chromosomes in the GnomAD database, including 392,106 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 (47888 hom., cov: 33)
  • Exomes 𝑓: 0.83 (344218 hom.)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21
• Publications: 10 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=-0.82).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANXA2	NM_004039.3	MANE Select	c.-11-65A>G		intron	N/A	NP_004030.1	P07355-1
	ANXA2	NM_001002858.3		c.44-65A>G		intron	N/A	NP_001002858.1	P07355-2
	ANXA2	NM_001002857.2		c.-11-65A>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.-11-65A>G		intron	N/A	ENSP00000387545.3	P07355-1
	ANXA2	ENST00000332680.8	TSL:1	c.44-65A>G		intron	N/A	ENSP00000346032.3	P07355-2
	ANXA2	ENST00000396024.7	TSL:1	c.-11-65A>G		intron	N/A	ENSP00000379342.3	P07355-1

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119656 AN: 152022 Hom.: 47862 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.795

GnomAD4 exome AF: 0.830 AC: 825044 AN: 994052 Hom.: 344218 Cov.: 13 AF XY: 0.834 AC XY: 427417 AN XY: 512586

African (AFR) AF: 0.632 AC: 14869 AN: 23534

American (AMR) AF: 0.870 AC: 31481 AN: 36170

Ashkenazi Jewish (ASJ) AF: 0.817 AC: 17880 AN: 21888

East Asian (EAS) AF: 1.00 AC: 37426 AN: 37440

South Asian (SAS) AF: 0.926 AC: 65646 AN: 70914

European-Finnish (FIN) AF: 0.862 AC: 44887 AN: 52066

Middle Eastern (MID) AF: 0.762 AC: 3679 AN: 4828

European-Non Finnish (NFE) AF: 0.815 AC: 572710 AN: 702584

Other (OTH) AF: 0.817 AC: 36466 AN: 44628

GnomAD4 genome AF: 0.787 AC: 119728 AN: 152140 Hom.: 47888 Cov.: 33 AF XY: 0.794 AC XY: 59057 AN XY: 74394

African (AFR) AF: 0.640 AC: 26535 AN: 41460

American (AMR) AF: 0.827 AC: 12650 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2788 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5164 AN: 5170

South Asian (SAS) AF: 0.938 AC: 4525 AN: 4824

European-Finnish (FIN) AF: 0.866 AC: 9170 AN: 10592

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.826 AC: 56139 AN: 68004

Other (OTH) AF: 0.797 AC: 1687 AN: 2116

Alfa AF: 0.819 Hom.: 25234

Bravo AF: 0.778

Asia WGS AF: 0.943 AC: 3278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.2
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: rs7182242; hg19: chr15-60678350;