11-988619-A-G

Position:

• chr11-988619-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_012305.4(AP2A2):​c.1199A>G​(p.Asn400Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,613,638 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0029 (12 hom.)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 8.90

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08468628).
• BP6: Variant 11-988619-A-G is Benign according to our data. Variant chr11-988619-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2641099.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 389 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.1199A>G	p.Asn400Ser	missense_variant	10/22	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.1199A>G	p.Asn400Ser	missense_variant	10/22	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.1202A>G	p.Asn401Ser	missense_variant	10/22	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.1202A>G		non_coding_transcript_exon_variant	10/21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.1199A>G		non_coding_transcript_exon_variant	10/21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.1199A>G		non_coding_transcript_exon_variant	10/21			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.1199A>G		non_coding_transcript_exon_variant	10/20			ENSP00000510648.1

Frequencies

GnomAD3 genomes AF: 0.00256 AC: 389 AN: 152212 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00399

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00429

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.00242 AC: 604 AN: 249080 Hom.: 4 AF XY: 0.00242 AC XY: 327 AN XY: 135162

Gnomad AFR exome AF: 0.000903

Gnomad AMR exome AF: 0.00264

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.000327

Gnomad NFE exome AF: 0.00404

Gnomad OTH exome AF: 0.00281

GnomAD4 exome AF: 0.00294 AC: 4291 AN: 1461308 Hom.: 12 Cov.: 31 AF XY: 0.00287 AC XY: 2089 AN XY: 726944

Gnomad4 AFR exome AF: 0.000836

Gnomad4 AMR exome AF: 0.00271

Gnomad4 ASJ exome AF: 0.000497

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000325

Gnomad4 FIN exome AF: 0.000622

Gnomad4 NFE exome AF: 0.00352

Gnomad4 OTH exome AF: 0.00222

GnomAD4 genome AF: 0.00255 AC: 389 AN: 152330 Hom.: 2 Cov.: 33 AF XY: 0.00243 AC XY: 181 AN XY: 74492

Gnomad4 AFR AF: 0.000721

Gnomad4 AMR AF: 0.00398

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00429

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00366 Hom.: 5

Bravo AF: 0.00256

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000461 AC: 2

ESP6500EA AF: 0.00410 AC: 35

ExAC AF: 0.00208 AC: 252

EpiCase AF: 0.00507

EpiControl AF: 0.00486

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

AP2A2: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	.;T
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.6	.;M
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Uncertain	0.31
Sift	Benign	0.067	T;T
Sift4G	Benign	0.087	T;T
Polyphen		0.99	D;D
Vest4		0.91
MVP		0.74
MPC		0.90
ClinPred		0.086	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.68

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: rs144441591; hg19: chr11-988619;