17-43883040-T-G

Position:

• chr17-43883040-T-G

Variant summary

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

The NM_005374.5(MPP2):​c.316A>C​(p.Thr106Pro) 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: 0.558

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]

MPP2 (HGNC:):

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/exons	MANE	Protein	UniProt
MPP2	NM_005374.5	c.316A>C	p.Thr106Pro	missense_variant	5/13	ENST00000269095.9	NP_005365.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9	c.316A>C	p.Thr106Pro	missense_variant	5/13	1	NM_005374.5	ENSP00000269095.4
MPP2	ENST00000461854.5	c.388A>C	p.Thr130Pro	missense_variant	6/14	1		ENSP00000428286.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.316A>C (p.T106P) alteration is located in exon 5 (coding exon 4) of the MPP2 gene. This alteration results from a A to C substitution at nucleotide position 316, causing the threonine (T) at amino acid position 106 to be replaced by a proline (P). 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	0.97
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;.;.;.;T;.;.;.;T;D;T;D;.;D;.;D;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;.;.;D;D;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP	Uncertain	0.095	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.60	T
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.7	D;D;D;.;.;.;D;D;D;D;.;D;D;D;D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.0040	D;D;D;.;.;.;D;D;D;D;.;D;D;D;D;D;.
Sift4G	Benign	0.13	T;T;T;T;T;T;T;T;T;.;T;D;D;.;.;D;.
Vest4		0.60
MutPred		0.57		.;.;.;.;.;.;Loss of phosphorylation at T130 (P = 0.0562);.;.;.;.;.;.;.;.;.;.;
MVP		0.85
MPC		1.7
ClinPred		0.96	D
GERP RS		4.0
gMVP		0.82

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: chr17-41960408;