rs7163836

Positions:

• chr15-60348029-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANXA2	NM_004039.3	c.961-340G>A		intron_variant		ENST00000451270.7	NP_004030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANXA2	ENST00000451270.7	c.961-340G>A		intron_variant		1	NM_004039.3	ENSP00000387545	P1

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

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.562

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.437

Alfa AF: 0.450 Hom.: 2952

Bravo AF: 0.443

Asia WGS AF: 0.504 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.55

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

Publications

LitVar

Other links and lift over

dbSNP: rs7163836; hg19: chr15-60640228;