NM_004039.3:c.778+70G>C

Variant names:

• chr15-60351654-C-G
• rs8037326
• NM_004039.3:c.778+70G>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.867 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.778+70G>C		intron	N/A	NP_004030.1	P07355-1
	ANXA2	NM_001002858.3		c.832+70G>C		intron	N/A	NP_001002858.1	P07355-2
	ANXA2	NM_001002857.2		c.778+70G>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.778+70G>C		intron	N/A	ENSP00000387545.3	P07355-1
	ANXA2	ENST00000332680.8	TSL:1	c.832+70G>C		intron	N/A	ENSP00000346032.3	P07355-2
	ANXA2	ENST00000396024.7	TSL:1	c.778+70G>C		intron	N/A	ENSP00000379342.3	P07355-1

Frequencies

GnomAD3 genomes AF: 0.790 AC: 120007 AN: 151980 Hom.: 47805 Cov.: 31

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.: 11 AF XY: 0.751 AC XY: 325554 AN XY: 433234

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

GnomAD4 genome AF: 0.790 AC: 120137 AN: 152098 Hom.: 47869 Cov.: 31 AF XY: 0.786 AC XY: 58423 AN XY: 74370

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

Alfa AF: 0.653 Hom.: 1284

Bravo AF: 0.809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.057
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)

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: rs8037326; hg19: chr15-60643853; COSMIC: COSV60315534; COSMIC: COSV60315534;