chr15-60348029-C-T

Variant names:

• chr15-60348029-C-T
• rs7163836
• NM_004039.3:c.961-340G>A

Variant summary

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

The NM_004039.3(ANXA2):​c.961-340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 152,010 control chromosomes in the GnomAD database, including 14,354 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 0.43 (14354 hom., cov: 32)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.577
• Publications: 6 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 (AMR) allele frequency at 95% confidence interval = 0.552 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.961-340G>A		intron	N/A	NP_004030.1
	ANXA2	NM_001002858.3		c.1015-340G>A		intron	N/A	NP_001002858.1
	ANXA2	NM_001002857.2		c.961-340G>A		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.961-340G>A		intron	N/A	ENSP00000387545.3
	ANXA2	ENST00000332680.8	TSL:1	c.1015-340G>A		intron	N/A	ENSP00000346032.3
	ANXA2	ENST00000396024.7	TSL:1	c.961-340G>A		intron	N/A	ENSP00000379342.3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65252 AN: 151892 Hom.: 14332 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.430 AC: 65313 AN: 152010 Hom.: 14354 Cov.: 32 AF XY: 0.432 AC XY: 32061 AN XY: 74292

African (AFR) AF: 0.404 AC: 16735 AN: 41444

American (AMR) AF: 0.562 AC: 8579 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1378 AN: 3470

East Asian (EAS) AF: 0.508 AC: 2622 AN: 5158

South Asian (SAS) AF: 0.457 AC: 2202 AN: 4816

European-Finnish (FIN) AF: 0.405 AC: 4281 AN: 10558

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 28026 AN: 67974

Other (OTH) AF: 0.437 AC: 923 AN: 2114

Alfa AF: 0.450 Hom.: 3030

Bravo AF: 0.443

Asia WGS AF: 0.504 AC: 1755 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	1.2
DANN	Benign	0.55
PhyloP100		-0.58
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: rs7163836; hg19: chr15-60640228;