chr2-218269415-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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]

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]

PNKD Gene-Disease associations (from GenCC):

• paroxysmal nonkinesigenic dyskinesia 1

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• Tourette syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.241G>A	p.Asp81Asn	missense	Exon 2 of 11	NP_001078.2	Q13685
	AAMP	NM_001302545.2		c.244G>A	p.Asp82Asn	missense	Exon 2 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.241G>A	p.Asp81Asn	missense	Exon 2 of 11	ENSP00000248450.4	Q13685
	AAMP	ENST00000444053.5	TSL:1	c.244G>A	p.Asp82Asn	missense	Exon 2 of 11	ENSP00000403343.1	C9JEH3
	AAMP	ENST00000896972.1		c.241G>A	p.Asp81Asn	missense	Exon 2 of 11	ENSP00000567031.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

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	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
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.4
PrimateAI	Uncertain	0.73	T
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.22
Sift	Benign	0.076	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	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
PromoterAI		0.014	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.37
gMVP		0.57
Mutation Taster		=22/78	disease causing

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

Other links and lift over

dbSNP: rs894396135; hg19: chr2-219134138;