2-218270142-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The ENST00000444053.5(AAMP):c.-56G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00703 in 1,594,102 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (43 hom.)
• Consequence: AAMP ENST00000444053.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.484

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 2-218270142-C-A is Benign according to our data. Variant chr2-218270142-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1203274.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AAMP	NM_001087.5			upstream_gene_variant		ENST00000248450.9
AAMP	NM_001302545.2			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAMP	ENST00000248450.9			upstream_gene_variant		1	NM_001087.5	A1

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 776 AN: 152238 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000941

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.000915

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00916

Gnomad OTH AF: 0.00287

GnomAD4 exome AF: 0.00724 AC: 10438 AN: 1441746 Hom.: 43 Cov.: 32 AF XY: 0.00717 AC XY: 5127 AN XY: 715556

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00189

Gnomad4 ASJ exome AF: 0.00372

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00392

Gnomad4 FIN exome AF: 0.00447

Gnomad4 NFE exome AF: 0.00842

Gnomad4 OTH exome AF: 0.00648

GnomAD4 genome AF: 0.00509 AC: 776 AN: 152356 Hom.: 6 Cov.: 32 AF XY: 0.00474 AC XY: 353 AN XY: 74502

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.000914

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00414

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00916

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00752 Hom.: 0

Bravo AF: 0.00474

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
Cadd	Benign	18
Dann	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs140903641; hg19: chr2-219134865;