rs1026477

Positions:

• chr11-30467480-G-A
• chr11-30467480-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001584.3(MPPED2):​c.536+27816C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,990 control chromosomes in the GnomAD database, including 16,706 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (16706 hom., cov: 31)
• Consequence: MPPED2 NM_001584.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23

Genes affected

MPPED2 (HGNC:1180): (metallophosphoesterase domain containing 2) Predicted to enable manganese ion binding activity; phosphoric diester hydrolase activity; and purine ribonucleotide binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPPED2	NM_001584.3	c.536+27816C>T		intron_variant		ENST00000358117.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPPED2	ENST00000358117.10	c.536+27816C>T		intron_variant		1	NM_001584.3	P1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68229 AN: 151872 Hom.: 16695 Cov.: 31

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.449 AC: 68277 AN: 151990 Hom.: 16706 Cov.: 31 AF XY: 0.453 AC XY: 33639 AN XY: 74284

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.424

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.464

Alfa AF: 0.505 Hom.: 25302

Bravo AF: 0.449

Asia WGS AF: 0.474 AC: 1647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.60

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: rs1026477; hg19: chr11-30489027;