4-40823714-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004307.2(APBB2):c.1862C>T(p.Ser621Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000403 in 1,613,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
APBB2
NM_004307.2 missense
NM_004307.2 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.56
Genes affected
APBB2 (HGNC:582): (amyloid beta precursor protein binding family B member 2) The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta (A4) precursor-like protein 2. This protein contains two phosphotyrosine binding (PTB) domains, which are thought to function in signal transduction. Polymorphisms in this gene have been associated with Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40504196).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
APBB2 | NM_004307.2 | c.1862C>T | p.Ser621Phe | missense_variant | 16/18 | ENST00000508593.6 | NP_004298.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
APBB2 | ENST00000508593.6 | c.1862C>T | p.Ser621Phe | missense_variant | 16/18 | 1 | NM_004307.2 | ENSP00000427211.1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152140Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249432Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135348
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461590Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 727126
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74332
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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 | Apr 15, 2024 | The c.1862C>T (p.S621F) alteration is located in exon 16 (coding exon 12) of the APBB2 gene. This alteration results from a C to T substitution at nucleotide position 1862, causing the serine (S) at amino acid position 621 to be replaced by a phenylalanine (F). 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
Uncertain
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;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.;.;.;.;.;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;D;N;N;D;N;D;N;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D;D;.;D;D;D
Polyphen
D;.;D;.;.;.;.;.;.;.;.
Vest4
MutPred
Loss of disorder (P = 0.0012);.;.;.;.;.;.;.;.;.;.;
MVP
MPC
1.3
ClinPred
T
GERP RS
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