11-30426076-C-T

Variant names:

• chr11-30426076-C-T
• rs2310798
• NM_001584.3:c.537-8443G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001584.3(MPPED2):​c.537-8443G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,122 control chromosomes in the GnomAD database, including 6,176 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 0.23 (6176 hom., cov: 32)
• Consequence: MPPED2 NM_001584.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73
• Publications: 4 publications found

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]

ENSG00000255480 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001584.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPED2	NM_001584.3	MANE Select	c.537-8443G>A		intron	N/A	NP_001575.1
	MPPED2	NM_001377952.1		c.537-8443G>A		intron	N/A	NP_001364881.1
	MPPED2	NM_001377953.1		c.537-8443G>A		intron	N/A	NP_001364882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPPED2	ENST00000358117.10	TSL:1 MANE Select	c.537-8443G>A		intron	N/A	ENSP00000350833.4
	MPPED2	ENST00000448418.6	TSL:1	c.537-8443G>A		intron	N/A	ENSP00000388258.2
	MPPED2	ENST00000526437.5	TSL:1	n.*281-8443G>A		intron	N/A	ENSP00000432469.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34244 AN: 152004 Hom.: 6165 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.225 AC: 34292 AN: 152122 Hom.: 6176 Cov.: 32 AF XY: 0.223 AC XY: 16609 AN XY: 74366

African (AFR) AF: 0.507 AC: 21015 AN: 41464

American (AMR) AF: 0.154 AC: 2350 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 455 AN: 3472

East Asian (EAS) AF: 0.185 AC: 957 AN: 5168

South Asian (SAS) AF: 0.160 AC: 772 AN: 4822

European-Finnish (FIN) AF: 0.0967 AC: 1023 AN: 10580

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7144 AN: 67994

Other (OTH) AF: 0.214 AC: 452 AN: 2114

Alfa AF: 0.131 Hom.: 1237

Bravo AF: 0.240

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.46
PhyloP100		-2.7
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: rs2310798; hg19: chr11-30447623;