2-218266579-C-G

Variant names:

• chr2-218266579-C-G
• rs1366028725
• NM_001087.5:c.543G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001087.5(AAMP):​c.543G>C​(p.Glu181Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AAMP NM_001087.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36
• Publications: 0 publications found

Genes affected

AAMP (HGNC:18): (angio associated migratory cell protein) The gene is a member of the immunoglobulin superfamily. The encoded protein is associated with angiogenesis, with potential roles in endothelial tube formation and the migration of endothelial cells. It may also regulate smooth muscle cell migration via the RhoA pathway. The encoded protein can bind to heparin and may mediate heparin-sensitive cell adhesion. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.246055).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001087.5. 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
	AAMP	NM_001087.5	MANE Select	c.543G>C	p.Glu181Asp	missense	Exon 5 of 11	NP_001078.2	Q13685
	AAMP	NM_001302545.2		c.546G>C	p.Glu182Asp	missense	Exon 5 of 11	NP_001289474.1	C9JEH3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAMP	ENST00000248450.9	TSL:1 MANE Select	c.543G>C	p.Glu181Asp	missense	Exon 5 of 11	ENSP00000248450.4	Q13685
	AAMP	ENST00000444053.5	TSL:1	c.546G>C	p.Glu182Asp	missense	Exon 5 of 11	ENSP00000403343.1	C9JEH3
	AAMP	ENST00000896972.1		c.534G>C	p.Glu178Asp	missense	Exon 5 of 11	ENSP00000567031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460722 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726572

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26092

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111494

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.054
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.68	N
PhyloP100		1.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.070
Sift	Benign	0.34	T
Sift4G	Benign	0.46	T
Polyphen		0.033	B
Vest4		0.50
MutPred		0.38		Loss of catalytic residue at E182 (P = 0.2107)
MVP		0.50
MPC		0.53
ClinPred		0.43	T
GERP RS		4.0
PromoterAI		0.0072	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.093
gMVP		0.67
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1366028725; hg19: chr2-219131302;