chr15-23643886-G-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_019066.5(MAGEL2):c.*107C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 1,276,374 control chromosomes in the GnomAD database, including 225,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.66 ( 34610 hom., cov: 33)
Exomes 𝑓: 0.58 ( 190982 hom. )
Consequence
MAGEL2
NM_019066.5 3_prime_UTR
NM_019066.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.215
Genes affected
MAGEL2 (HGNC:6814): (MAGE family member L2) Prader-Willi syndrome (PWS) is caused by the loss of expression of imprinted genes in chromosome 15q11-q13 region. Affected individuals exhibit neonatal hypotonia, developmental delay, and childhood-onset obesity. Necdin (NDN), a gene involved in the terminal differentiation of neurons, localizes to this region of the genome and has been implicated as one of the genes responsible for the etiology of PWS. This gene is structurally similar to NDN, is also localized to the PWS chromosomal region, and is paternally imprinted, suggesting a possible role for it in PWS. [provided by RefSeq, Oct 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 15-23643886-G-T is Benign according to our data. Variant chr15-23643886-G-T is described in ClinVar as [Benign]. Clinvar id is 1252492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAGEL2 | NM_019066.5 | c.*107C>A | 3_prime_UTR_variant | 1/1 | ENST00000650528.1 | NP_061939.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAGEL2 | ENST00000650528.1 | c.*107C>A | 3_prime_UTR_variant | 1/1 | NM_019066.5 | ENSP00000497810 | P1 |
Frequencies
GnomAD3 genomes AF: 0.662 AC: 100608AN: 151988Hom.: 34569 Cov.: 33
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GnomAD4 exome AF: 0.577 AC: 649203AN: 1124268Hom.: 190982 Cov.: 15 AF XY: 0.580 AC XY: 316346AN XY: 545482
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GnomAD4 genome AF: 0.662 AC: 100711AN: 152106Hom.: 34610 Cov.: 33 AF XY: 0.668 AC XY: 49703AN XY: 74364
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at