chr15-23643886-G-T

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.215
Variant links:
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]

Genome browser will be placed here

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
MAGEL2NM_019066.5 linkuse as main transcriptc.*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
MAGEL2ENST00000650528.1 linkuse as main transcriptc.*107C>A 3_prime_UTR_variant 1/1 NM_019066.5 ENSP00000497810 P1

Frequencies

GnomAD3 genomes
AF:
0.662
AC:
100608
AN:
151988
Hom.:
34569
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.840
Gnomad AMI
AF:
0.632
Gnomad AMR
AF:
0.668
Gnomad ASJ
AF:
0.603
Gnomad EAS
AF:
0.776
Gnomad SAS
AF:
0.765
Gnomad FIN
AF:
0.595
Gnomad MID
AF:
0.650
Gnomad NFE
AF:
0.550
Gnomad OTH
AF:
0.663
GnomAD4 exome
AF:
0.577
AC:
649203
AN:
1124268
Hom.:
190982
Cov.:
15
AF XY:
0.580
AC XY:
316346
AN XY:
545482
show subpopulations
Gnomad4 AFR exome
AF:
0.853
Gnomad4 AMR exome
AF:
0.688
Gnomad4 ASJ exome
AF:
0.592
Gnomad4 EAS exome
AF:
0.787
Gnomad4 SAS exome
AF:
0.750
Gnomad4 FIN exome
AF:
0.589
Gnomad4 NFE exome
AF:
0.547
Gnomad4 OTH exome
AF:
0.618
GnomAD4 genome
AF:
0.662
AC:
100711
AN:
152106
Hom.:
34610
Cov.:
33
AF XY:
0.668
AC XY:
49703
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.840
Gnomad4 AMR
AF:
0.669
Gnomad4 ASJ
AF:
0.603
Gnomad4 EAS
AF:
0.776
Gnomad4 SAS
AF:
0.766
Gnomad4 FIN
AF:
0.595
Gnomad4 NFE
AF:
0.550
Gnomad4 OTH
AF:
0.663
Alfa
AF:
0.577
Hom.:
32579
Bravo
AF:
0.673
Asia WGS
AF:
0.780
AC:
2712
AN:
3478

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJul 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.37
DANN
Benign
0.64

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: rs9785; hg19: chr15-23889033; API