rs2233068

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_019066.5(MAGEL2):c.2886C>T(p.Ser962Ser) 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:7

Conservation

PhyloP100: -0.163

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

Schaaf-Yang syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Illumina, Labcorp Genetics (formerly Invitae), ClinGen

MAGEL2 links:

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new If you want to explore the variant's impact on the transcript NM_019066.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.011).

BP6

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

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 492 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019066.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEL2	NM_019066.5	MANE Select	c.2886C>T	p.Ser962Ser	synonymous	Exon 1 of 1	NP_061939.3	Q9UJ55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAGEL2	ENST00000650528.1	MANE Select	c.2886C>T	p.Ser962Ser	synonymous	Exon 1 of 1	ENSP00000497810.1	Q9UJ55

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

GnomAD2 exomes

AF:

0.00543

AC:

1334

AN:

245862

AF XY:

0.00650

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 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

African (AFR)

AF:

0.000866

AC:

AN:

33470

American (AMR)

AF:

0.00181

AC:

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0131

AC:

342

AN:

26126

East Asian (EAS)

AF:

0.000151

AC:

AN:

39696

South Asian (SAS)

AF:

0.0211

AC:

1819

AN:

86248

European-Finnish (FIN)

AF:

0.00180

AC:

AN:

51810

Middle Eastern (MID)

AF:

0.0153

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00299

AC:

3325

AN:

1111774

Other (OTH)

AF:

0.00484

AC:

292

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

385

769

1154

1538

1923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00323

AC:

492

AN:

152260

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

290

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41558

American (AMR)

AF:

0.00372

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0132

AC:

AN:

3472

East Asian (EAS)

AF:

0.000970

AC:

AN:

5156

South Asian (SAS)

AF:

0.0199

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00348

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00318

AC:

216

AN:

68010

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.4

(source)

DANN

Benign

0.72

PhyloP100

-0.16

Mutation Taster

=100/0

polymorphism

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over