17-43884083-C-T

Variant names:

• chr17-43884083-C-T
• rs231518
• NM_005374.5:c.151-728G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PVS1_Moderate BA1

The NM_001278372.2(MPP2):​c.222+1G>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 702,314 control chromosomes in the GnomAD database, including 5,916 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 0.12 (1147 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4769 hom.)
• Consequence: MPP2 NM_001278372.2 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

Genes affected

MPP2 (HGNC:7220): (MAGUK p55 scaffold protein 2) Palmitoylated membrane protein 2 is a member of a family of membrane-associated proteins termed MAGUKs (membrane-associated guanylate kinase homologs). MAGUKs interact with the cytoskeleton and regulate cell proliferation, signaling pathways, and intracellular junctions. Palmitoylated membrane protein 2 contains a conserved sequence, called the SH3 (src homology 3) motif, found in several other proteins that associate with the cytoskeleton and are suspected to play important roles in signal transduction. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.041594453 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP2	NM_005374.5	c.151-728G>A		intron_variant	Intron 3 of 12	ENST00000269095.9	NP_005365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9	c.151-728G>A		intron_variant	Intron 3 of 12	1	NM_005374.5	ENSP00000269095.4
MPP2	ENST00000461854.5	c.222+1G>A		splice_donor_variant, intron_variant	Intron 4 of 13	1		ENSP00000428286.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17627 AN: 152082 Hom.: 1146 Cov.: 32

Gnomad AFR AF: 0.0989

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.000960

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.122 AC: 66965 AN: 550114 Hom.: 4769 Cov.: 0 AF XY: 0.122 AC XY: 36313 AN XY: 297780

Gnomad4 AFR exome AF: 0.104 AC: 1636 AN: 15802

Gnomad4 AMR exome AF: 0.0669 AC: 2317 AN: 34652

Gnomad4 ASJ exome AF: 0.177 AC: 3540 AN: 20012

Gnomad4 EAS exome AF: 0.000218 AC: 7 AN: 32086

Gnomad4 SAS exome AF: 0.0969 AC: 6065 AN: 62608

Gnomad4 FIN exome AF: 0.156 AC: 5245 AN: 33592

Gnomad4 NFE exome AF: 0.138 AC: 43837 AN: 316702

Gnomad4 Remaining exome AF: 0.120 AC: 3676 AN: 30590

GnomAD4 genome AF: 0.116 AC: 17628 AN: 152200 Hom.: 1147 Cov.: 32 AF XY: 0.114 AC XY: 8507 AN XY: 74400

Gnomad4 AFR AF: 0.0988 AC: 0.0988439 AN: 0.0988439

Gnomad4 AMR AF: 0.0856 AC: 0.0855779 AN: 0.0855779

Gnomad4 ASJ AF: 0.175 AC: 0.174539 AN: 0.174539

Gnomad4 EAS AF: 0.000962 AC: 0.000962279 AN: 0.000962279

Gnomad4 SAS AF: 0.0907 AC: 0.0907015 AN: 0.0907015

Gnomad4 FIN AF: 0.145 AC: 0.14507 AN: 0.14507

Gnomad4 NFE AF: 0.136 AC: 0.135832 AN: 0.135832

Gnomad4 OTH AF: 0.114 AC: 0.114218 AN: 0.114218

Alfa AF: 0.126 Hom.: 1027

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs231518; hg19: chr17-41961451;