rs543947750

Variant names:

• chr17-43882288-C-A
• rs543947750
• NM_005374.5:c.677G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-43882288-C-A
• chr17-43882288-C-G
• chr17-43882288-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005374.5(MPP2):​c.677G>T​(p.Arg226Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPP2 NM_005374.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36917156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP2	NM_005374.5	c.677G>T	p.Arg226Leu	missense_variant	Exon 6 of 13	ENST00000269095.9	NP_005365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9	c.677G>T	p.Arg226Leu	missense_variant	Exon 6 of 13	1	NM_005374.5	ENSP00000269095.4
MPP2	ENST00000461854.5	c.749G>T	p.Arg250Leu	missense_variant	Exon 7 of 14	1		ENSP00000428286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	.;.;.;.;T;.;.;.;.;T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D;.;.;D;D;D;D;D;.;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.37	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.0	N;N;N;.;.;.;N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.49	T;T;T;.;.;.;T;T;T;T
Sift4G	Benign	0.31	T;T;T;T;T;T;T;T;T;T
Vest4		0.70
MutPred		0.49		.;.;.;.;.;.;Loss of ubiquitination at K255 (P = 0.1355);.;.;.;
MVP		0.60
MPC		1.1
ClinPred		0.29	T
GERP RS		3.6
gMVP		0.68

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: rs543947750; hg19: chr17-41959656;