11-996522-C-G

Position:

• chr11-996522-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012305.4(AP2A2):​c.1956+2277C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: AP2A2 NM_012305.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.1956+2277C>G		intron_variant		ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.1956+2277C>G		intron_variant		1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.1959+2277C>G		intron_variant		1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.1959+2277C>G		intron_variant		2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.1956+2277C>G		intron_variant				ENSP00000508951.1
AP2A2	ENST00000687890.1	n.1956+2277C>G		intron_variant				ENSP00000510756.1
AP2A2	ENST00000693238.1	n.1956+2277C>G		intron_variant				ENSP00000510648.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.86
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs4077293; hg19: chr11-996522;