9-127108096-GGG-CAA

Variant names:

• chr9-127108096-GGG-CAA
• NM_012098.3:c.634_636delCCCinsTTG
• ANGPTL2 p.Pro212Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_012098.3(ANGPTL2):​c.634_636delCCCinsTTG​(p.Pro212Leu) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ANGPTL2 NM_012098.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.69
• Publications: 0 publications found

Genes affected

ANGPTL2 (HGNC:490): (angiopoietin like 2) Angiopoietins are members of the vascular endothelial growth factor family and the only known growth factors largely specific for vascular endothelium. Angiopoietin-1, angiopoietin-2, and angiopoietin-4 participate in the formation of blood vessels. ANGPTL2 protein is a secreted glycoprotein with homology to the angiopoietins and may exert a function on endothelial cells through autocrine or paracrine action. [provided by RefSeq, Jul 2008]

RALGPS1 (HGNC:16851): (Ral GEF with PH domain and SH3 binding motif 1) Enables guanyl-nucleotide exchange factor activity. Involved in regulation of Ral protein signal transduction. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012098.3. 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
	ANGPTL2	NM_012098.3	MANE Select	c.634_636delCCCinsTTG	p.Pro212Leu	missense	N/A	NP_036230.1	Q9UKU9-1
	RALGPS1	NM_014636.3	MANE Select	c.610+38740_610+38742delGGGinsCAA		intron	N/A	NP_055451.1	Q5JS13-1
	RALGPS1	NM_001322325.2		c.610+38740_610+38742delGGGinsCAA		intron	N/A	NP_001309254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL2	ENST00000373425.8	TSL:1 MANE Select	c.634_636delCCCinsTTG	p.Pro212Leu	missense	N/A	ENSP00000362524.3	Q9UKU9-1
	RALGPS1	ENST00000259351.10	TSL:1 MANE Select	c.610+38740_610+38742delGGGinsCAA		intron	N/A	ENSP00000259351.5	Q5JS13-1
	RALGPS1	ENST00000373434.5	TSL:1	c.610+38740_610+38742delGGGinsCAA		intron	N/A	ENSP00000362533.1	Q5JS13-2

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.7

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: chr9-129870375;