rs9785

Variant names:

• chr15-23643886-G-T
• rs9785
• NM_019066.5:c.*107C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-23643886-G-T
• chr15-23643886-G-A
• chr15-23643886-G-C

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.*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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.215
• Publications: 10 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=-0.92).
• BP6: Variant 15-23643886-G-T is Benign according to our data. Variant chr15-23643886-G-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.*107C>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.*107C>A		3_prime_UTR	Exon 1 of 1	ENSP00000497810.1	Q9UJ55

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

African (AFR) AF: 0.853 AC: 21853 AN: 25630

American (AMR) AF: 0.688 AC: 11385 AN: 16556

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 10438 AN: 17630

East Asian (EAS) AF: 0.787 AC: 26537 AN: 33714

South Asian (SAS) AF: 0.750 AC: 35741 AN: 47656

European-Finnish (FIN) AF: 0.589 AC: 20622 AN: 35030

Middle Eastern (MID) AF: 0.654 AC: 2813 AN: 4302

European-Non Finnish (NFE) AF: 0.547 AC: 490157 AN: 895732

Other (OTH) AF: 0.618 AC: 29657 AN: 48018

GnomAD4 genome AF: 0.662 AC: 100711 AN: 152106 Hom.: 34610 Cov.: 33 AF XY: 0.668 AC XY: 49703 AN XY: 74364

African (AFR) AF: 0.840 AC: 34873 AN: 41530

American (AMR) AF: 0.669 AC: 10225 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2092 AN: 3470

East Asian (EAS) AF: 0.776 AC: 4013 AN: 5170

South Asian (SAS) AF: 0.766 AC: 3690 AN: 4820

European-Finnish (FIN) AF: 0.595 AC: 6289 AN: 10578

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.550 AC: 37369 AN: 67942

Other (OTH) AF: 0.663 AC: 1401 AN: 2114

Alfa AF: 0.601 Hom.: 69806

Bravo AF: 0.673

Asia WGS AF: 0.780 AC: 2712 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	-0.92
CADD	Benign	0.37
DANN	Benign	0.64
PhyloP100		-0.21
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: rs9785; hg19: chr15-23889033;