rs7483870

Positions:

• chr11-976019-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_012305.4(AP2A2):​c.474-1076G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,210 control chromosomes in the GnomAD database, including 2,913 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 0.17 (2913 hom., cov: 33)
• Consequence: AP2A2 NM_012305.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.474-1076G>A		intron_variant		ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.474-1076G>A		intron_variant		1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.474-1076G>A		intron_variant		1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.474-1076G>A		intron_variant		2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.474-1076G>A		intron_variant				ENSP00000508951.1
AP2A2	ENST00000687890.1	n.474-1076G>A		intron_variant				ENSP00000510756.1
AP2A2	ENST00000693238.1	n.474-1076G>A		intron_variant				ENSP00000510648.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26530 AN: 152092 Hom.: 2910 Cov.: 33

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.174 AC: 26535 AN: 152210 Hom.: 2913 Cov.: 33 AF XY: 0.176 AC XY: 13076 AN XY: 74404

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.285

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.187

Alfa AF: 0.218 Hom.: 5038

Bravo AF: 0.173

Asia WGS AF: 0.163 AC: 564 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.24		Position offset: 21

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7483870; hg19: chr11-976019;