Variant rs2281680 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003917.5(AP1G2):c.1092-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,612,872 control chromosomes in the GnomAD database, including 28,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1844 hom., cov: 32)

Exomes 𝑓: 0.19 ( 26537 hom. )

Consequence

AP1G2
NM_003917.5 splice_region, intron

Scores

Splicing: ADA: 0.00004158

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.566

Variant links:

Genes affected

AP1G2 (HGNC:556): (adaptor related protein complex 1 subunit gamma 2) Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. The adaptin family of proteins is composed of four classes of molecules named alpha, beta-, beta prime- and gamma- adaptins. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. The protein encoded by this gene is a gamma-adaptin protein and it belongs to the adaptor complexes large subunits family. This protein along with the complex is thought to function at some trafficking step in the complex pathways between the trans-Golgi network and the cell surface. [provided by RefSeq, Aug 2017]

AP1G2 links:

AP1G2 (HGNC:):

AP1G2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP1G2	NM_003917.5 linkuse as main transcript	c.1092-5G>A		splice_region_variant, intron_variant		ENST00000397120.8	NP_003908.1	O75843

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP1G2	ENST00000397120.8 linkuse as main transcript	c.1092-5G>A		splice_region_variant, intron_variant		1	NM_003917.5	ENSP00000380309.3		O75843

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20795

AN:

152106

Hom.:

1835

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0340

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.156

Gnomad EAS

AF:

0.125

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.0974

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.178

AC:

44014

AN:

247360

Hom.:

4474

AF XY:

0.186

AC XY:

24948

AN XY:

133968

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.118

Gnomad SAS exome

AF:

0.297

Gnomad FIN exome

AF:

0.104

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.186

AC:

271706

AN:

1460646

Hom.:

26537

Cov.:

AF XY:

0.190

AC XY:

137898

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.0282

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.139

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.188

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.137

AC:

20815

AN:

152226

Hom.:

1844

Cov.:

AF XY:

0.136

AC XY:

10111

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0339

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.156

Gnomad4 EAS

AF:

0.125

Gnomad4 SAS

AF:

0.299

Gnomad4 FIN

AF:

0.0974

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.182

Hom.:

5316

Bravo

AF:

0.136

Asia WGS

AF:

0.228

AC:

792

AN:

3478

EpiCase

AF:

0.187

EpiControl

AF:

0.191

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.4

DANN

Benign

0.88

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.012

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over