NM_012305.4:c.676G>T

Variant names:

• chr11-981270-G-T
• NM_012305.4:c.676G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012305.4(AP2A2):​c.676G>T​(p.Val226Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,110 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.676G>T	p.Val226Leu	missense_variant	Exon 6 of 22	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.676G>T	p.Val226Leu	missense_variant	Exon 6 of 22	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.676G>T	p.Val226Leu	missense_variant	Exon 6 of 22	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.676G>T		non_coding_transcript_exon_variant	Exon 6 of 21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.676G>T		non_coding_transcript_exon_variant	Exon 6 of 21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.676G>T		non_coding_transcript_exon_variant	Exon 6 of 21			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.676G>T		non_coding_transcript_exon_variant	Exon 6 of 20			ENSP00000510648.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461110 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;T;T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.56	D;D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	M;.;.;M
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-2.2	N;N;D;N
REVEL	Benign	0.21
Sift	Benign	0.087	T;T;T;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.95	P;.;.;P
Vest4		0.68
MutPred		0.46		Gain of loop (P = 0.069);.;Gain of loop (P = 0.069);Gain of loop (P = 0.069);
MVP		0.55
MPC		0.78
ClinPred		0.80	D
GERP RS		3.1
Varity_R		0.12
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-981270;