rs7943115

Variant names:

• chr11-973885-T-C
• rs7943115
• NM_012305.4:c.473+1630T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-973885-T-C
• chr11-973885-T-G

Variant summary

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

The NM_012305.4(AP2A2):​c.473+1630T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,042 control chromosomes in the GnomAD database, including 26,662 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 0.58 (26662 hom., cov: 33)
• Consequence: AP2A2 NM_012305.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.808
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012305.4. 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
	AP2A2	NM_012305.4	MANE Select	c.473+1630T>C		intron	N/A	NP_036437.1	O94973-1
	AP2A2	NM_001242837.2		c.473+1630T>C		intron	N/A	NP_001229766.1	O94973-2
	AP2A2	NR_144509.2		n.625+1630T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2A2	ENST00000448903.7	TSL:1 MANE Select	c.473+1630T>C		intron	N/A	ENSP00000413234.3	O94973-1
	AP2A2	ENST00000332231.9	TSL:1	c.473+1630T>C		intron	N/A	ENSP00000327694.5	O94973-2
	AP2A2	ENST00000528815.5	TSL:2	n.473+1630T>C		intron	N/A	ENSP00000431630.1	O94973-3

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88714 AN: 151924 Hom.: 26647 Cov.: 33

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.584 AC: 88768 AN: 152042 Hom.: 26662 Cov.: 33 AF XY: 0.580 AC XY: 43079 AN XY: 74334

African (AFR) AF: 0.494 AC: 20473 AN: 41444

American (AMR) AF: 0.710 AC: 10855 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2102 AN: 3470

East Asian (EAS) AF: 0.317 AC: 1641 AN: 5176

South Asian (SAS) AF: 0.421 AC: 2030 AN: 4824

European-Finnish (FIN) AF: 0.601 AC: 6348 AN: 10566

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.637 AC: 43277 AN: 67956

Other (OTH) AF: 0.632 AC: 1334 AN: 2112

Alfa AF: 0.503 Hom.: 1514

Bravo AF: 0.589

Asia WGS AF: 0.428 AC: 1492 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.60
DANN	Benign	0.71
PhyloP100		-0.81
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: rs7943115; hg19: chr11-973885;