NM_005374.5:c.1270G>A

Variant names:

• chr17-43879865-C-T
• rs2047025935
• NM_005374.5:c.1270G>A

Variant summary

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

The NM_005374.5(MPP2):​c.1270G>A​(p.Gly424Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,068 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: MPP2 NM_005374.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12

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.1270G>A	p.Gly424Ser	missense_variant	Exon 11 of 13	ENST00000269095.9	NP_005365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9	c.1270G>A	p.Gly424Ser	missense_variant	Exon 11 of 13	1	NM_005374.5	ENSP00000269095.4
MPP2	ENST00000461854.5	c.1342G>A	p.Gly448Ser	missense_variant	Exon 12 of 14	1		ENSP00000428286.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152068 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152068 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74266

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.043	T
BayesDel_noAF	Benign	-0.30
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	.;.;.;.;T;.;.;.;.;T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.90	D;.;.;D;D;D;D;D;.;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.96	T
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.2	D;D;D;.;.;.;D;D;D;D
REVEL	Benign	0.26
Sift	Uncertain	0.021	D;D;D;.;.;.;D;D;D;D
Sift4G	Uncertain	0.054	T;T;T;T;T;T;D;D;T;D
Vest4		0.64
MutPred		0.77		.;Gain of sheet (P = 0.0344);.;Gain of sheet (P = 0.0344);.;.;.;.;.;.;
MVP		0.72
MPC		1.2
ClinPred		0.97	D
GERP RS		3.9
gMVP		0.86

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: rs2047025935; hg19: chr17-41957233;