Variant rs2233068 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_019066.5(MAGEL2):c.2886C>T(p.Ser962=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,612,178 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 58 hom. )

Consequence

MAGEL2
NM_019066.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.163

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]

MAGEL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 15-23644857-G-A is Benign according to our data. Variant chr15-23644857-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-23644857-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.163 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00323 (492/152260) while in subpopulation SAS AF= 0.0199 (96/4820). AF 95% confidence interval is 0.0167. There are 3 homozygotes in gnomad4. There are 290 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 492 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAGEL2	NM_019066.5 linkuse as main transcript	c.2886C>T	p.Ser962=	synonymous_variant	1/1	ENST00000650528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAGEL2	ENST00000650528.1 linkuse as main transcript	c.2886C>T	p.Ser962=	synonymous_variant	1/1		NM_019066.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

490

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0132

Gnomad EAS

AF:

0.000774

Gnomad SAS

AF:

0.0195

Gnomad FIN

AF:

0.00348

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00543

AC:

1334

AN:

245862

Hom.:

AF XY:

0.00650

AC XY:

871

AN XY:

133930

show subpopulations

Gnomad AFR exome

AF:

0.000527

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.000336

Gnomad SAS exome

AF:

0.0204

Gnomad FIN exome

AF:

0.00221

Gnomad NFE exome

AF:

0.00398

Gnomad OTH exome

AF:

0.00366

GnomAD4 exome

AF:

0.00416

AC:

6075

AN:

1459918

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

3474

AN XY:

726312

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.00181

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0211

Gnomad4 FIN exome

AF:

0.00180

Gnomad4 NFE exome

AF:

0.00299

Gnomad4 OTH exome

AF:

0.00484

GnomAD4 genome

AF:

0.00323

AC:

492

AN:

152260

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

290

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.0132

Gnomad4 EAS

AF:

0.000970

Gnomad4 SAS

AF:

0.0199

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00390

Hom.:

Bravo

AF:

0.00283

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.00409

EpiControl

AF:

0.00398

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	May 01, 2024	MAGEL2: BP4, BP7, BS1, BS2 -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 30, 2019	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.4

DANN

Benign

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over