rs8920

Variant names:

• chr15-23643744-A-T
• rs8920
• NM_019066.5:c.*249T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-23643744-A-T
• chr15-23643744-A-C
• chr15-23643744-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019066.5(MAGEL2):​c.*249T>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 0.626 in 402,118 control chromosomes in the GnomAD database, including 82,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.67 (36244 hom., cov: 33)
  • Exomes 𝑓: 0.60 (46009 hom.)
• Consequence: MAGEL2 NM_019066.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.50
• Publications: 7 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Illumina

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-23643744-A-T is Benign according to our data. Variant chr15-23643744-A-T is described in ClinVar as Benign. ClinVar VariationId is 1233500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

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.*249T>A		3_prime_UTR	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.*249T>A		3_prime_UTR	Exon 1 of 1	ENSP00000497810.1	Q9UJ55

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102506 AN: 151984 Hom.: 36201 Cov.: 33

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.669

GnomAD4 exome AF: 0.597 AC: 149225 AN: 250016 Hom.: 46009 Cov.: 3 AF XY: 0.595 AC XY: 74958 AN XY: 126020

African (AFR) AF: 0.887 AC: 6490 AN: 7316

American (AMR) AF: 0.684 AC: 5941 AN: 8690

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 5321 AN: 9094

East Asian (EAS) AF: 0.793 AC: 17078 AN: 21548

South Asian (SAS) AF: 0.746 AC: 4142 AN: 5552

European-Finnish (FIN) AF: 0.582 AC: 10786 AN: 18540

Middle Eastern (MID) AF: 0.629 AC: 795 AN: 1264

European-Non Finnish (NFE) AF: 0.548 AC: 88494 AN: 161608

Other (OTH) AF: 0.620 AC: 10178 AN: 16404

GnomAD4 genome AF: 0.675 AC: 102611 AN: 152102 Hom.: 36244 Cov.: 33 AF XY: 0.680 AC XY: 50566 AN XY: 74352

African (AFR) AF: 0.884 AC: 36700 AN: 41532

American (AMR) AF: 0.673 AC: 10290 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2089 AN: 3470

East Asian (EAS) AF: 0.777 AC: 4010 AN: 5158

South Asian (SAS) AF: 0.766 AC: 3697 AN: 4824

European-Finnish (FIN) AF: 0.595 AC: 6278 AN: 10560

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37377 AN: 67956

Other (OTH) AF: 0.668 AC: 1407 AN: 2106

Alfa AF: 0.620 Hom.: 3607

Bravo AF: 0.686

Asia WGS AF: 0.782 AC: 2717 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.81
DANN	Benign	0.75
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8920; hg19: chr15-23888891;