rs10751667

Variant names:

• chr11-941941-A-T
• rs10751667
• NM_012305.4:c.67+15853A>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.67+15853A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 148,856 control chromosomes in the GnomAD database, including 29,955 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 0.63 (29955 hom., cov: 29)
• Consequence: AP2A2 NM_012305.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• Publications: 16 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.67+15853A>T		intron_variant	Intron 1 of 21	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.67+15853A>T		intron_variant	Intron 1 of 21	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.67+15853A>T		intron_variant	Intron 1 of 21	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.67+15853A>T		intron_variant	Intron 1 of 20	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.67+15853A>T		intron_variant	Intron 1 of 20			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.67+15853A>T		intron_variant	Intron 1 of 20			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.67+15853A>T		intron_variant	Intron 1 of 19			ENSP00000510648.1

Frequencies

GnomAD3 genomes AF: 0.634 AC: 94364 AN: 148742 Hom.: 29922 Cov.: 29

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.557

Gnomad AMR AF: 0.728

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.317

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.757

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.672

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

GnomAD4 genome AF: 0.635 AC: 94457 AN: 148856 Hom.: 29955 Cov.: 29 AF XY: 0.630 AC XY: 45742 AN XY: 72640

African (AFR) AF: 0.651 AC: 26383 AN: 40520

American (AMR) AF: 0.728 AC: 10982 AN: 15078

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2098 AN: 3416

East Asian (EAS) AF: 0.318 AC: 1520 AN: 4782

South Asian (SAS) AF: 0.433 AC: 1998 AN: 4610

European-Finnish (FIN) AF: 0.612 AC: 6295 AN: 10284

Middle Eastern (MID) AF: 0.750 AC: 213 AN: 284

European-Non Finnish (NFE) AF: 0.644 AC: 43077 AN: 66928

Other (OTH) AF: 0.675 AC: 1404 AN: 2080

Alfa AF: 0.630 Hom.: 3762

Bravo AF: 0.636

Asia WGS AF: 0.438 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.89
DANN	Benign	0.42
PhyloP100		-1.5
PromoterAI		-0.020	Neutral
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: rs10751667; hg19: chr11-941941; COSMIC: COSV59964419; COSMIC: COSV59964419;