rs12979830

Variant names:

• chr19-49793895-T-G
• rs12979830
• NM_130787.3:c.705+803T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_130787.3(AP2A1):​c.705+803T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: AP2A1 NM_130787.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.224

Genes affected

AP2A1 (HGNC:561): (adaptor related protein complex 2 subunit alpha 1) This gene encodes the alpha 1 adaptin subunit of the adaptor protein 2 (AP-2) complex found in clathrin coated vesicles. The AP-2 complex is a heterotetramer consisting of two large adaptins (alpha or beta), a medium adaptin (mu), and a small adaptin (sigma). The complex is part of the protein coat on the cytoplasmic face of coated vesicles which links clathrin to receptors in vesicles. Alternative splicing of this gene results in two transcript variants encoding two different isoforms. A third transcript variant has been described, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AP2A1	NM_130787.3	c.705+803T>G		intron_variant	Intron 6 of 22	ENST00000354293.10	NP_570603.2
AP2A1	NM_014203.3	c.705+803T>G		intron_variant	Intron 6 of 23		NP_055018.2
AP2A1	XM_011526556.3	c.756+803T>G		intron_variant	Intron 6 of 23		XP_011524858.1
AP2A1	XM_011526557.4	c.756+803T>G		intron_variant	Intron 6 of 22		XP_011524859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AP2A1	ENST00000354293.10	c.705+803T>G		intron_variant	Intron 6 of 22	1	NM_130787.3	ENSP00000346246.4
AP2A1	ENST00000359032.10	c.705+803T>G		intron_variant	Intron 6 of 23	5		ENSP00000351926.4
AP2A1	ENST00000597774.5	n.*43+803T>G		intron_variant	Intron 4 of 21	5		ENSP00000472492.1
AP2A1	ENST00000600199.1	n.832+803T>G		intron_variant	Intron 6 of 7	5

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs12979830; hg19: chr19-50297152;