2-218270142-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

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

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.484
Variant links:
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]

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ACMG classification

Classification made for transcript

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 GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AAMPNM_001087.5 linkuse as main transcript upstream_gene_variant ENST00000248450.9 NP_001078.2
AAMPNM_001302545.2 linkuse as main transcript upstream_gene_variant NP_001289474.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AAMPENST00000248450.9 linkuse as main transcript upstream_gene_variant 1 NM_001087.5 ENSP00000248450 A1

Frequencies

GnomAD3 genomes
AF:
0.00510
AC:
776
AN:
152238
Hom.:
6
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs140903641; hg19: chr2-219134865; API