11-959457-ATA-GTC

Variant names:

• chr11-959457-ATA-GTC
• NM_012305.4:c.88_90delATAinsGTC
• AP2A2 p.Ile30Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_012305.4(AP2A2):​c.88_90delATAinsGTC​(p.Ile30Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I30L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: AP2A2 NM_012305.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.99
• Publications: 0 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 0 ACMG points.

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.88_90delATAinsGTC	p.Ile30Val	missense	N/A	NP_036437.1	O94973-1
	AP2A2	NM_001242837.2		c.88_90delATAinsGTC	p.Ile30Val	missense	N/A	NP_001229766.1	O94973-2
	AP2A2	NR_144509.2		n.240_242delATAinsGTC		non_coding_transcript_exon	Exon 2 of 21

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AP2A2	ENST00000448903.7	TSL:1 MANE Select	c.88_90delATAinsGTC	p.Ile30Val	missense	N/A	ENSP00000413234.3	O94973-1
	AP2A2	ENST00000332231.9	TSL:1	c.88_90delATAinsGTC	p.Ile30Val	missense	N/A	ENSP00000327694.5	O94973-2
	AP2A2	ENST00000528815.5	TSL:2	n.88_90delATAinsGTC		non_coding_transcript_exon	Exon 2 of 21	ENSP00000431630.1	O94973-3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-959457;