17-35605801-G-T

Position:

• chr17-35605801-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001030006.2(AP2B1):​c.240G>T​(p.Gln80His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AP2B1 NM_001030006.2 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.62

Genes affected

AP2B1 (HGNC:563): (adaptor related protein complex 2 subunit beta 1) The protein encoded by this gene is one of two large chain components of the assembly protein complex 2, which serves to link clathrin to receptors in coated vesicles. The encoded protein is found on the cytoplasmic face of coated vesicles in the plasma membrane. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AP2B1	NM_001030006.2	c.240G>T	p.Gln80His	missense_variant	4/22	ENST00000610402.5	NP_001025177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AP2B1	ENST00000610402.5	c.240G>T	p.Gln80His	missense_variant	4/22	1	NM_001030006.2	ENSP00000483185.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

Variant interpretted as Uncertain significance and reported on 09-23-2019 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.;T;.;T;T;.;T;T;T;.;.
Eigen	Benign	-0.020
Eigen_PC	Benign	0.11
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.98	D;D;D;D;D;.;.;.;D;D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T;T;D;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	.;.;L;.;.;.;L;.;.;.;L;.
PrimateAI	Pathogenic	0.90	D
Sift4G	Benign	0.40	T;T;T;T;T;T;T;T;D;T;T;T
Polyphen		0.52, 0.12	.;.;P;.;.;.;B;.;.;.;B;.
Vest4		0.66, 0.68, 0.67, 0.67
MutPred		0.59		Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);Gain of ubiquitination at K78 (P = 0.0882);
MVP		0.91
ClinPred		0.73	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.75

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: rs2073654935; hg19: chr17-33932820;