NM_005374.5:c.1499G>C

Variant names:

• chr17-43877967-C-G
• rs761519494
• NM_005374.5:c.1499G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005374.5(MPP2):​c.1499G>C​(p.Arg500Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,026 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MPP2 NM_005374.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.806

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPP2	NM_005374.5	c.1499G>C	p.Arg500Pro	missense_variant	Exon 13 of 13	ENST00000269095.9	NP_005365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9	c.1499G>C	p.Arg500Pro	missense_variant	Exon 13 of 13	1	NM_005374.5	ENSP00000269095.4
MPP2	ENST00000461854.5	c.1571G>C	p.Arg524Pro	missense_variant	Exon 14 of 14	1		ENSP00000428286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000404 AC: 1 AN: 247806 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134220

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461026 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	.;.;.;.;T;.;.;.;.;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Pathogenic	0.99	D;.;.;D;D;D;D;D;.;D
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.7	D;D;D;.;.;.;D;D;D;D
REVEL	Benign	0.18
Sift	Uncertain	0.0050	D;D;D;.;.;.;D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D;D;D;D;D;D
Vest4		0.53
MutPred		0.49		.;Loss of MoRF binding (P = 0.0719);.;Loss of MoRF binding (P = 0.0719);.;.;.;.;.;.;
MVP		0.72
MPC		1.8
ClinPred		0.88	D
GERP RS		4.2
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761519494; hg19: chr17-41955335;