11-977100-C-T

Variant names:

• chr11-977100-C-T
• rs1159376146
• NM_012305.4:c.479C>T

Variant summary

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

The NM_012305.4(AP2A2):​c.479C>T​(p.Thr160Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05

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.479C>T	p.Thr160Ile	missense_variant	Exon 5 of 22	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.479C>T	p.Thr160Ile	missense_variant	Exon 5 of 22	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.479C>T	p.Thr160Ile	missense_variant	Exon 5 of 22	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.479C>T		non_coding_transcript_exon_variant	Exon 5 of 21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.479C>T		non_coding_transcript_exon_variant	Exon 5 of 21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.479C>T		non_coding_transcript_exon_variant	Exon 5 of 21			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.479C>T		non_coding_transcript_exon_variant	Exon 5 of 20			ENSP00000510648.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	.;T;T;T;.;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T;T;T;T;T;.
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L;.;L;.;.;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D;D;T;T;D
Sift4G	Uncertain	0.0050	D;D;D;D;D;D
Polyphen		0.99	D;.;D;.;.;.
Vest4		0.76
MutPred		0.47		Loss of disorder (P = 0.0557);Loss of disorder (P = 0.0557);Loss of disorder (P = 0.0557);.;.;.;
MVP		0.64
MPC		1.1
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.60
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1159376146; hg19: chr11-977100;