11-981282-G-A

Position:

• chr11-981282-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.688G>A	p.Val230Ile	missense_variant	6/22	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.688G>A	p.Val230Ile	missense_variant	6/22	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.688G>A	p.Val230Ile	missense_variant	6/22	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.688G>A		non_coding_transcript_exon_variant	6/21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.688G>A		non_coding_transcript_exon_variant	6/21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.688G>A		non_coding_transcript_exon_variant	6/21			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.688G>A		non_coding_transcript_exon_variant	6/20			ENSP00000510648.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2022

The c.688G>A (p.V230I) alteration is located in exon 6 (coding exon 6) of the AP2A2 gene. This alteration results from a G to A substitution at nucleotide position 688, causing the valine (V) at amino acid position 230 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;.;D;D
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.59	N;.;.;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.36	T;T;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.99	D;.;.;B
Vest4		0.41
MutPred		0.60		Gain of catalytic residue at V230 (P = 0.0608);.;Gain of catalytic residue at V230 (P = 0.0608);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-981282;