rs10751667

chr11-941941-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	UniProt
AP2A2	NM_012305.4	c.67+15853A>T		intron_variant		ENST00000448903.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AP2A2	ENST00000448903.7	c.67+15853A>T		intron_variant		1	NM_012305.4	A1

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

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.728

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.644

Gnomad4 OTH AF: 0.675

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

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: rs10751667; hg19: chr11-941941; COSMIC: COSV59964419; COSMIC: COSV59964419;