17-35650692-A-G

Variant summary

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

The NM_001030006.2(AP2B1):ā€‹c.1699A>Gā€‹(p.Ile567Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000889 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000089 ( 0 hom. )

Consequence

AP2B1
NM_001030006.2 missense

Scores

2
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.31
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
AP2B1NM_001030006.2 linkuse as main transcriptc.1699A>G p.Ile567Val missense_variant 13/22 ENST00000610402.5 NP_001025177.1 P63010-2A0A140VJE8Q96EL6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
AP2B1ENST00000610402.5 linkuse as main transcriptc.1699A>G p.Ile567Val missense_variant 13/221 NM_001030006.2 ENSP00000483185.1 P63010-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251462
Hom.:
0
AF XY:
0.0000441
AC XY:
6
AN XY:
135904
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000615
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000889
AC:
13
AN:
1461892
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727248
show subpopulations
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:
0.0000187
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.000144
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.0000576
AC:
7

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 07, 2023The c.1699A>G (p.I567V) alteration is located in exon 13 (coding exon 12) of the AP2B1 gene. This alteration results from a A to G substitution at nucleotide position 1699, causing the isoleucine (I) at amino acid position 567 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.34
BayesDel_addAF
Benign
-0.024
T
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.41
.;T;.;T;T;.;T;T;.;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D;D;D;D;.;.;.;D;D;D
M_CAP
Benign
0.0027
T
MetaRNN
Uncertain
0.51
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
.;M;.;.;.;M;.;.;M;.
PrimateAI
Uncertain
0.75
T
Sift4G
Benign
0.31
T;T;T;T;T;T;T;T;T;D
Polyphen
0.27, 0.21
.;B;.;.;.;B;.;.;B;.
Vest4
0.38, 0.41, 0.40, 0.40
MutPred
0.49
Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);.;.;Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);.;
MVP
0.70
ClinPred
0.70
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.40

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

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

Other links and lift over

dbSNP: rs763799850; hg19: chr17-33977711; API