11-996522-C-T

Variant names:

• chr11-996522-C-T
• rs4077293
• NM_012305.4:c.1956+2277C>T

Variant summary

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

The NM_012305.4(AP2A2):​c.1956+2277C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,028 control chromosomes in the GnomAD database, including 8,819 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 0.33 (8819 hom., cov: 32)
• Consequence: AP2A2 NM_012305.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 6 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 (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.1956+2277C>T		intron_variant	Intron 14 of 21	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.1956+2277C>T		intron_variant	Intron 14 of 21	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.1959+2277C>T		intron_variant	Intron 14 of 21	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.1959+2277C>T		intron_variant	Intron 14 of 20	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.1956+2277C>T		intron_variant	Intron 14 of 20			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.1956+2277C>T		intron_variant	Intron 14 of 20			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.1956+2277C>T		intron_variant	Intron 14 of 19			ENSP00000510648.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50385 AN: 151910 Hom.: 8812 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.353

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.332 AC: 50411 AN: 152028 Hom.: 8819 Cov.: 32 AF XY: 0.333 AC XY: 24720 AN XY: 74316

African (AFR) AF: 0.257 AC: 10652 AN: 41436

American (AMR) AF: 0.497 AC: 7583 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1249 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1427 AN: 5162

South Asian (SAS) AF: 0.254 AC: 1226 AN: 4820

European-Finnish (FIN) AF: 0.329 AC: 3475 AN: 10566

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23687 AN: 67994

Other (OTH) AF: 0.351 AC: 737 AN: 2102

Alfa AF: 0.346 Hom.: 34510

Bravo AF: 0.341

Asia WGS AF: 0.285 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.76
PhyloP100		-0.42
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)		0.0		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: rs4077293; hg19: chr11-996522;