chr15-60364483-GCG-TCC

Variant names:

• chr15-60364483-GCG-TCC
• NM_004039.3:c.187_189delCGCinsGGA
• ANXA2 p.Arg63Gly

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_004039.3(ANXA2):​c.187_189delCGCinsGGA​(p.Arg63Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R63H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ANXA2 NM_004039.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.51
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.187_189delCGCinsGGA	p.Arg63Gly	missense	N/A	NP_004030.1	P07355-1
	ANXA2	NM_001002858.3		c.241_243delCGCinsGGA	p.Arg81Gly	missense	N/A	NP_001002858.1	P07355-2
	ANXA2	NM_001002857.2		c.187_189delCGCinsGGA	p.Arg63Gly	missense	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.187_189delCGCinsGGA	p.Arg63Gly	missense	N/A	ENSP00000387545.3	P07355-1
	ANXA2	ENST00000332680.8	TSL:1	c.241_243delCGCinsGGA	p.Arg81Gly	missense	N/A	ENSP00000346032.3	P07355-2
	ANXA2	ENST00000396024.7	TSL:1	c.187_189delCGCinsGGA	p.Arg63Gly	missense	N/A	ENSP00000379342.3	P07355-1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr15-60656682;