dbSNP rs920483294: AP2A1:p.Phe361Leu (chr19-49799444-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_130787.3(AP2A1):c.1083C>A(p.Phe361Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,616 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AP2A1
NM_130787.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

Publications

0 publications found

Variant links:

Genes affected

AP2A1 (HGNC:561): (adaptor related protein complex 2 subunit alpha 1) This gene encodes the alpha 1 adaptin subunit of the adaptor protein 2 (AP-2) complex found in clathrin coated vesicles. The AP-2 complex is a heterotetramer consisting of two large adaptins (alpha or beta), a medium adaptin (mu), and a small adaptin (sigma). The complex is part of the protein coat on the cytoplasmic face of coated vesicles which links clathrin to receptors in vesicles. Alternative splicing of this gene results in two transcript variants encoding two different isoforms. A third transcript variant has been described, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]

AP2A1 links:

ENSG00000297022 (HGNC:):

ENSG00000297022 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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_130787.3. 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
	AP2A1	NM_130787.3	MANE Select	c.1083C>A	p.Phe361Leu	missense	Exon 9 of 23	NP_570603.2
	AP2A1	NM_014203.3		c.1083C>A	p.Phe361Leu	missense	Exon 9 of 24	NP_055018.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AP2A1	ENST00000354293.10	TSL:1 MANE Select	c.1083C>A	p.Phe361Leu	missense	Exon 9 of 23	ENSP00000346246.4	O95782-2
AP2A1	ENST00000359032.10	TSL:5	c.1083C>A	p.Phe361Leu	missense	Exon 9 of 24	ENSP00000351926.4	O95782-1
AP2A1	ENST00000597774.5	TSL:5	n.*421C>A		non_coding_transcript_exon	Exon 7 of 22	ENSP00000472492.1	M0R2D9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459616

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726028

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33450

American (AMR)

AF:

0.00

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

86030

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111340

Other (OTH)

AF:

0.00

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Benign

0.0090

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.82

MutationAssessor

Benign

2.0

PhyloP100

1.9

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.28

Sift

Benign

0.65

Sift4G

Benign

0.65

Polyphen

1.0

Vest4

0.62

MutPred

0.45

Loss of helix (P = 0.079)

MVP

0.65

MPC

1.4

ClinPred

0.90

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.41

gMVP

0.68

Mutation Taster

=36/64

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over