17-43906130-G-A

Position:

• chr17-43906130-G-A

Variant summary

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

The NM_005374.5(MPP2):​c.-34+1344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 975,616 control chromosomes in the GnomAD database, including 68,494 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 0.43 (14826 hom., cov: 32)
  • Exomes 𝑓: 0.36 (53668 hom.)
• Consequence: MPP2 NM_005374.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPP2	NM_005374.5	c.-34+1344C>T		intron_variant		ENST00000269095.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPP2	ENST00000269095.9	c.-34+1344C>T		intron_variant		1	NM_005374.5	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65399 AN: 151638 Hom.: 14802 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.403

GnomAD4 exome AF: 0.355 AC: 292627 AN: 823860 Hom.: 53668 Cov.: 29 AF XY: 0.356 AC XY: 135307 AN XY: 380562

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.626

Gnomad4 ASJ exome AF: 0.359

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.549

Gnomad4 FIN exome AF: 0.327

Gnomad4 NFE exome AF: 0.345

Gnomad4 OTH exome AF: 0.390

GnomAD4 genome AF: 0.431 AC: 65460 AN: 151756 Hom.: 14826 Cov.: 32 AF XY: 0.439 AC XY: 32526 AN XY: 74150

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.407

Alfa AF: 0.402 Hom.: 1601

Bravo AF: 0.445

Asia WGS AF: 0.629 AC: 2190 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs231480; hg19: chr17-41983498;