17-35650692-A-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001030006.2(AP2B1):āc.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
NM_001030006.2 missense
Scores
2
6
8
Clinical Significance
Conservation
PhyloP100: 9.31
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]
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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 |
---|---|---|---|---|---|---|---|---|
AP2B1 | NM_001030006.2 | c.1699A>G | p.Ile567Val | missense_variant | 13/22 | ENST00000610402.5 | NP_001025177.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AP2B1 | ENST00000610402.5 | c.1699A>G | p.Ile567Val | missense_variant | 13/22 | 1 | NM_001030006.2 | ENSP00000483185.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251462Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135904
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GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461892Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727248
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GnomAD4 genome Cov.: 32
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32
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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 submitter | clinical testing | Ambry Genetics | Feb 07, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
.;T;.;T;T;.;T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;.;.;.;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.;.;M;.;.;M;.
PrimateAI
Uncertain
T
Sift4G
Benign
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
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
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at