11-981282-G-A

Variant names:

• chr11-981282-G-A
• NM_012305.4:c.688G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012305.4(AP2A2):​c.688G>A​(p.Val230Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.81
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36713374).

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.688G>A	p.Val230Ile	missense	Exon 6 of 22	NP_036437.1	O94973-1
	AP2A2	NM_001242837.2		c.688G>A	p.Val230Ile	missense	Exon 6 of 22	NP_001229766.1	O94973-2
	AP2A2	NR_144509.2		n.840G>A		non_coding_transcript_exon	Exon 6 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2A2	ENST00000448903.7	TSL:1 MANE Select	c.688G>A	p.Val230Ile	missense	Exon 6 of 22	ENSP00000413234.3	O94973-1
	AP2A2	ENST00000332231.9	TSL:1	c.688G>A	p.Val230Ile	missense	Exon 6 of 22	ENSP00000327694.5	O94973-2
	AP2A2	ENST00000528815.5	TSL:2	n.688G>A		non_coding_transcript_exon	Exon 6 of 21	ENSP00000431630.1	O94973-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	24
DANN	Benign	0.83
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.59	N
PhyloP100		9.8
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.18
Sift	Benign	0.36	T
Sift4G	Benign	0.49	T
Polyphen		0.99	D
Vest4		0.41
MutPred		0.60		Gain of catalytic residue at V230 (P = 0.0608)
MVP		0.52
MPC		0.62
ClinPred		0.49	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.035
gMVP		0.37
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr11-981282;