rs7943115

chr11-973885-T-Cchr11-973885-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AP2A2	NM_012305.4	c.473+1630T>C		intron_variant		ENST00000448903.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP2A2	ENST00000448903.7	c.473+1630T>C		intron_variant		1	NM_012305.4	A1

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

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.710

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.317

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.632

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.60
Dann	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs7943115; hg19: chr11-973885;