2-218269415-C-T

Variant names:

• chr2-218269415-C-T
• rs894396135
• NM_001087.5:c.241G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001087.5(AAMP):​c.241G>A​(p.Asp81Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AAMP NM_001087.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.40

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]

PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AAMP	NM_001087.5	c.241G>A	p.Asp81Asn	missense_variant	Exon 2 of 11	ENST00000248450.9	NP_001078.2
AAMP	NM_001302545.2	c.244G>A	p.Asp82Asn	missense_variant	Exon 2 of 11		NP_001289474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AAMP	ENST00000248450.9	c.241G>A	p.Asp81Asn	missense_variant	Exon 2 of 11	1	NM_001087.5	ENSP00000248450.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.241G>A (p.D81N) alteration is located in exon 2 (coding exon 2) of the AAMP gene. This alteration results from a G to A substitution at nucleotide position 241, causing the aspartic acid (D) at amino acid position 81 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T;.;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	M;.;.;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.6	D;D;D;D
REVEL	Benign	0.22
Sift	Benign	0.076	T;T;T;T
Sift4G	Uncertain	0.0090	D;D;D;.
Polyphen		1.0	D;D;D;.
Vest4		0.79
MutPred		0.36		.;Loss of phosphorylation at S84 (P = 0.0929);.;.;
MVP		0.62
MPC		1.4
ClinPred		0.99	D
GERP RS		4.5
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.37
gMVP		0.57

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: rs894396135; hg19: chr2-219134138;