rs1128413

chr11-1010694-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012305.4(AP2A2):c.*69C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 1,314,352 control chromosomes in the GnomAD database, including 184,334 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19304 hom., cov: 34)
  • Exomes 𝑓: 0.53 (165030 hom.)
• Consequence: AP2A2 NM_012305.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67

Genes affected

AP2A2 (HGNC:562): (adaptor related protein complex 2 subunit alpha 2) The protein encoded by this gene is a subunit of the AP-2 adaptor protein complex, which is involved in linking lipid and protein membrane components with the clathrin lattice. This interaction supports the formation of clathrin-coated vesicles, and the encoded subunit aids in the process by binding polyphosphoinositide-containing lipids in the cell membrane. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.078744E-5).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP2A2	NM_012305.4	c.*69C>T		3_prime_UTR_variant	22/22	ENST00000448903.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP2A2	ENST00000448903.7	c.*69C>T		3_prime_UTR_variant	22/22	1	NM_012305.4	A1

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74990 AN: 151964 Hom.: 19291 Cov.: 34

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.524

GnomAD3 exomes AF: 0.513 AC: 80756 AN: 157326 Hom.: 21681 AF XY: 0.501 AC XY: 41786 AN XY: 83434

Gnomad AFR exome AF: 0.362

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.301

Gnomad SAS exome AF: 0.376

Gnomad FIN exome AF: 0.532

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.556

GnomAD4 exome AF: 0.526 AC: 611751 AN: 1162270 Hom.: 165030 Cov.: 16 AF XY: 0.520 AC XY: 304106 AN XY: 584258

Gnomad4 AFR exome AF: 0.354

Gnomad4 AMR exome AF: 0.669

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.336

Gnomad4 SAS exome AF: 0.372

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.547

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.493 AC: 75038 AN: 152082 Hom.: 19304 Cov.: 34 AF XY: 0.492 AC XY: 36583 AN XY: 74336

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.550

Gnomad4 OTH AF: 0.528

Alfa AF: 0.526 Hom.: 14618

Bravo AF: 0.498

TwinsUK AF: 0.540 AC: 2002

ALSPAC AF: 0.543 AC: 2092

ExAC AF: 0.393 AC: 37098

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.66
Cadd	Benign	6.1
Dann	Benign	0.73
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.000011	T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P;P
PROVEAN	Benign	0.29	N
REVEL	Benign	0.040
Sift	Pathogenic	0.0	D
Vest4		0.21
ClinPred		0.023	T
GERP RS		0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1128413; hg19: chr11-1010694; COSMIC: COSV59961513; COSMIC: COSV59961513;