15-60380752-T-C

Position:

• chr15-60380752-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004039.3(ANXA2):​c.148+1590A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.62 (27850 hom., cov: 19)
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANXA2	NM_004039.3	c.148+1590A>G		intron_variant		ENST00000451270.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANXA2	ENST00000451270.7	c.148+1590A>G		intron_variant		1	NM_004039.3	P1

Frequencies

GnomAD3 genomes AF: 0.619 AC: 88144 AN: 142346 Hom.: 27829 Cov.: 19

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.723

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.619 AC: 88199 AN: 142416 Hom.: 27850 Cov.: 19 AF XY: 0.623 AC XY: 42642 AN XY: 68500

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.629

Alfa AF: 0.414 Hom.: 1024

Bravo AF: 0.622

Asia WGS AF: 0.528 AC: 1839 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.49

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: rs12909425; hg19: chr15-60672951;