17-43879309-G-T

Variant names:

• chr17-43879309-G-T
• NM_005374.5:c.1448C>A

Variant summary

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

The NM_005374.5(MPP2):​c.1448C>A​(p.Ala483Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPP2 NM_005374.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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.1448C>A	p.Ala483Glu	missense_variant	Exon 12 of 13	ENST00000269095.9	NP_005365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9	c.1448C>A	p.Ala483Glu	missense_variant	Exon 12 of 13	1	NM_005374.5	ENSP00000269095.4
MPP2	ENST00000461854.5	c.1520C>A	p.Ala507Glu	missense_variant	Exon 13 of 14	1		ENSP00000428286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1448C>A (p.A483E) alteration is located in exon 12 (coding exon 11) of the MPP2 gene. This alteration results from a C to A substitution at nucleotide position 1448, causing the alanine (A) at amino acid position 483 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	.;.;.;.;T;.;.;.;.;T
Eigen	Benign	0.11
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.91	D;.;.;D;D;D;D;D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.50	D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N;N;N;.;.;.;N;N;N;N
REVEL	Benign	0.15
Sift	Uncertain	0.019	D;D;D;.;.;.;D;D;D;D
Sift4G	Benign	0.066	T;T;T;T;T;T;T;T;T;T
Vest4		0.55
MutPred		0.54		.;Gain of disorder (P = 0.0321);.;Gain of disorder (P = 0.0321);.;.;.;.;.;.;
MVP		0.67
MPC		1.6
ClinPred		0.88	D
GERP RS		3.9
gMVP		0.92

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-41956677;