15-23643886-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
MAGEL2	NM_019066.5	c.*107C>A		3_prime_UTR_variant	1/1	ENST00000650528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEL2	ENST00000650528.1	c.*107C>A		3_prime_UTR_variant	1/1		NM_019066.5	P1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100608 AN: 151988 Hom.: 34569 Cov.: 33

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

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

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

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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

Other links and lift over

dbSNP: rs9785; hg19: chr15-23889033;