rs10861360
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_018171.5(APPL2):c.1813-181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 574,800 control chromosomes in the GnomAD database, including 6,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.18 ( 3451 hom., cov: 32)
Exomes 𝑓: 0.11 ( 3340 hom. )
Consequence
APPL2
NM_018171.5 intron
NM_018171.5 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.381
Genes affected
APPL2 (HGNC:18242): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) The protein encoded by this gene is one of two effectors of the small GTPase RAB5A/Rab5, which are involved in a signal transduction pathway. Both effectors contain an N-terminal Bin/Amphiphysin/Rvs (BAR) domain, a central pleckstrin homology (PH) domain, and a C-terminal phosphotyrosine binding (PTB) domain, and they bind the Rab5 through the BAR domain. They are associated with endosomal membranes and can be translocated to the nucleus in response to the EGF stimulus. They interact with the NuRD/MeCP1 complex (nucleosome remodeling and deacetylase /methyl-CpG-binding protein 1 complex) and are required for efficient cell proliferation. A chromosomal aberration t(12;22)(q24.1;q13.3) involving this gene and the PSAP2 gene results in 22q13.3 deletion syndrome, also known as Phelan-McDermid syndrome. [provided by RefSeq, Oct 2011]
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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=-0.7).
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APPL2 | NM_018171.5 | c.1813-181G>A | intron_variant | ENST00000258530.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APPL2 | ENST00000258530.8 | c.1813-181G>A | intron_variant | 1 | NM_018171.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.178 AC: 27033AN: 151988Hom.: 3429 Cov.: 32
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GnomAD3 exomes AF: 0.136 AC: 4283AN: 31528Hom.: 323 AF XY: 0.130 AC XY: 2321AN XY: 17838
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GnomAD4 exome AF: 0.111 AC: 46805AN: 422694Hom.: 3340 Cov.: 4 AF XY: 0.110 AC XY: 24789AN XY: 225232
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GnomAD4 genome ? AF: 0.178 AC: 27098AN: 152106Hom.: 3451 Cov.: 32 AF XY: 0.179 AC XY: 13278AN XY: 74366
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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