NM_012305.4:c.5C>T

Variant names:

• chr11-926026-C-T
• NM_012305.4:c.5C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_012305.4(AP2A2):​c.5C>T​(p.Pro2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000716 in 1,257,822 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: 31)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP2A2	NM_012305.4	c.5C>T	p.Pro2Leu	missense_variant	Exon 1 of 22	ENST00000448903.7	NP_036437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A2	ENST00000448903.7	c.5C>T	p.Pro2Leu	missense_variant	Exon 1 of 22	1	NM_012305.4	ENSP00000413234.3
AP2A2	ENST00000332231.9	c.5C>T	p.Pro2Leu	missense_variant	Exon 1 of 22	1		ENSP00000327694.5
AP2A2	ENST00000528815.5	n.5C>T		non_coding_transcript_exon_variant	Exon 1 of 21	2		ENSP00000431630.1
AP2A2	ENST00000687792.1	n.5C>T		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000508951.1
AP2A2	ENST00000687890.1	n.5C>T		non_coding_transcript_exon_variant	Exon 1 of 21			ENSP00000510756.1
AP2A2	ENST00000693238.1	n.5C>T		non_coding_transcript_exon_variant	Exon 1 of 20			ENSP00000510648.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000716 AC: 9 AN: 1257822 Hom.: 0 Cov.: 30 AF XY: 0.00000806 AC XY: 5 AN XY: 620130

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: 0.00000898

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	.;T;T
Eigen	Benign	-0.068
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Pathogenic	0.75	D
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.8	L;.;L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;.;D
Vest4		0.29
MutPred		0.39		Loss of catalytic residue at P2 (P = 0.0051);Loss of catalytic residue at P2 (P = 0.0051);Loss of catalytic residue at P2 (P = 0.0051);
MVP		0.74
MPC		1.8
ClinPred		1.0	D
GERP RS		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.70
gMVP		0.49

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: chr11-926026;