11-977100-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T160S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.05
• Publications: 1 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 2 ACMG points.

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

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.479C>T	p.Thr160Ile	missense	Exon 5 of 22	NP_036437.1	O94973-1
	AP2A2	NM_001242837.2		c.479C>T	p.Thr160Ile	missense	Exon 5 of 22	NP_001229766.1	O94973-2
	AP2A2	NR_144509.2		n.631C>T		non_coding_transcript_exon	Exon 5 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2A2	ENST00000448903.7	TSL:1 MANE Select	c.479C>T	p.Thr160Ile	missense	Exon 5 of 22	ENSP00000413234.3	O94973-1
	AP2A2	ENST00000332231.9	TSL:1	c.479C>T	p.Thr160Ile	missense	Exon 5 of 22	ENSP00000327694.5	O94973-2
	AP2A2	ENST00000528815.5	TSL:2	n.479C>T		non_coding_transcript_exon	Exon 5 of 21	ENSP00000431630.1	O94973-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.17
Eigen_PC	Benign	0.071
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.074	D
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		6.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.99	D
Vest4		0.76
MutPred		0.47		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
Mutation Taster		=41/59	disease causing

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

Other links and lift over

dbSNP: rs1159376146; hg19: chr11-977100;