15-60392977-G-T

Variant names:

• chr15-60392977-G-T
• rs11631777
• NM_004039.3:c.-12+4966C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004039.3(ANXA2):​c.-12+4966C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANXA2 NM_004039.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.935
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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.-12+4966C>A		intron	N/A	NP_004030.1
	ANXA2	NM_001002858.3		c.43+4894C>A		intron	N/A	NP_001002858.1
	ANXA2	NM_001002857.2		c.-12+4281C>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.-12+4966C>A		intron	N/A	ENSP00000387545.3
	ANXA2	ENST00000332680.8	TSL:1	c.43+4894C>A		intron	N/A	ENSP00000346032.3
	ANXA2	ENST00000396024.7	TSL:1	c.-116-2660C>A		intron	N/A	ENSP00000379342.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1051232 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 511730

African (AFR) AF: 0.00 AC: 0 AN: 20686

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11834

East Asian (EAS) AF: 0.00 AC: 0 AN: 11494

South Asian (SAS) AF: 0.00 AC: 0 AN: 60502

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3934

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 879664

Other (OTH) AF: 0.00 AC: 0 AN: 37792

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 5115

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.21
DANN	Benign	0.47
PhyloP100		-0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11631777; hg19: chr15-60685176;