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
• Publications: 20 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278372.2. 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
	MPP2	NM_005374.5	MANE Select	c.151-728G>A		intron	N/A	NP_005365.4
	MPP2	NM_001278370.2		c.286-728G>A		intron	N/A	NP_001265299.1	A0A0C4DH75
	MPP2	NM_001278372.2		c.222+1G>A		splice_donor intron	N/A	NP_001265301.1	D3DX49

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPP2	ENST00000269095.9	TSL:1 MANE Select	c.151-728G>A		intron	N/A	ENSP00000269095.4	D3DX48
	MPP2	ENST00000461854.5	TSL:1	c.222+1G>A		splice_donor intron	N/A	ENSP00000428286.1	D3DX49
	MPP2	ENST00000377184.7	TSL:1	c.202-728G>A		intron	N/A	ENSP00000366389.3	A0A0A0MRU0

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

African (AFR) AF: 0.104 AC: 1636 AN: 15802

American (AMR) AF: 0.0669 AC: 2317 AN: 34652

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 3540 AN: 20012

East Asian (EAS) AF: 0.000218 AC: 7 AN: 32086

South Asian (SAS) AF: 0.0969 AC: 6065 AN: 62608

European-Finnish (FIN) AF: 0.156 AC: 5245 AN: 33592

Middle Eastern (MID) AF: 0.158 AC: 642 AN: 4070

European-Non Finnish (NFE) AF: 0.138 AC: 43837 AN: 316702

Other (OTH) 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

African (AFR) AF: 0.0988 AC: 4104 AN: 41520

American (AMR) AF: 0.0856 AC: 1309 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 606 AN: 3472

East Asian (EAS) AF: 0.000962 AC: 5 AN: 5196

South Asian (SAS) AF: 0.0907 AC: 437 AN: 4818

European-Finnish (FIN) AF: 0.145 AC: 1536 AN: 10588

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9236 AN: 67996

Other (OTH) AF: 0.114 AC: 241 AN: 2110

Alfa AF: 0.126 Hom.: 1027

Bravo AF: 0.111

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.3
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs231518; hg19: chr17-41961451;