chr11-1010694-C-T

Variant names:

• chr11-1010694-C-T
• rs1128413
• ENST00000528815.5:n.*754C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000528815.5(AP2A2):​n.*754C>T variant causes a non coding transcript exon 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 ENST00000528815.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.67
• Publications: 23 publications found

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]

AP2A2 Gene-Disease associations (from GenCC):

• schizophrenia

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.*69C>T		3_prime_UTR_variant	Exon 22 of 22	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000528815.5	n.*754C>T		non_coding_transcript_exon_variant	Exon 21 of 21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.*783C>T		non_coding_transcript_exon_variant	Exon 21 of 21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.*754C>T		non_coding_transcript_exon_variant	Exon 21 of 21			ENSP00000510756.1
AP2A2	ENST00000688963.1	n.*501C>T		non_coding_transcript_exon_variant	Exon 8 of 8			ENSP00000510620.1
AP2A2	ENST00000693238.1	n.*1484C>T		non_coding_transcript_exon_variant	Exon 20 of 20			ENSP00000510648.1
AP2A2	ENST00000448903.7	c.*69C>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.*69C>T		3_prime_UTR_variant	Exon 22 of 22	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.*754C>T		3_prime_UTR_variant	Exon 21 of 21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.*783C>T		3_prime_UTR_variant	Exon 21 of 21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.*754C>T		3_prime_UTR_variant	Exon 21 of 21			ENSP00000510756.1
AP2A2	ENST00000688963.1	n.*501C>T		3_prime_UTR_variant	Exon 8 of 8			ENSP00000510620.1
AP2A2	ENST00000693238.1	n.*1484C>T		3_prime_UTR_variant	Exon 20 of 20			ENSP00000510648.1

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

GnomAD2 exomes AF: 0.513 AC: 80756 AN: 157326 AF XY: 0.501

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 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

African (AFR) AF: 0.354 AC: 9555 AN: 26964

American (AMR) AF: 0.669 AC: 23814 AN: 35570

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 12099 AN: 23766

East Asian (EAS) AF: 0.336 AC: 11677 AN: 34748

South Asian (SAS) AF: 0.372 AC: 27776 AN: 74654

European-Finnish (FIN) AF: 0.536 AC: 25744 AN: 48020

Middle Eastern (MID) AF: 0.547 AC: 2774 AN: 5074

European-Non Finnish (NFE) AF: 0.547 AC: 472089 AN: 863214

Other (OTH) AF: 0.522 AC: 26223 AN: 50260

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

African (AFR) AF: 0.373 AC: 15471 AN: 41462

American (AMR) AF: 0.640 AC: 9777 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1778 AN: 3472

East Asian (EAS) AF: 0.308 AC: 1592 AN: 5176

South Asian (SAS) AF: 0.379 AC: 1825 AN: 4820

European-Finnish (FIN) AF: 0.517 AC: 5470 AN: 10574

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37393 AN: 67984

Other (OTH) AF: 0.528 AC: 1114 AN: 2108

Alfa AF: 0.528 Hom.: 20519

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
PhyloP100		1.7
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1128413; hg19: chr11-1010694; COSMIC: COSV59961513; COSMIC: COSV59961513;