17-43881247-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000269095.9(MPP2):ā€‹c.916T>Cā€‹(p.Ser306Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

MPP2
ENST00000269095.9 missense

Scores

6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.28570002).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MPP2NM_005374.5 linkuse as main transcriptc.916T>C p.Ser306Pro missense_variant 8/13 ENST00000269095.9 NP_005365.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MPP2ENST00000269095.9 linkuse as main transcriptc.916T>C p.Ser306Pro missense_variant 8/131 NM_005374.5 ENSP00000269095 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461808
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 21, 2024The c.916T>C (p.S306P) alteration is located in exon 8 (coding exon 7) of the MPP2 gene. This alteration results from a T to C substitution at nucleotide position 916, causing the serine (S) at amino acid position 306 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
Benign
0.11
BayesDel_addAF
Uncertain
0.075
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.026
.;.;.;.;T;.;.;.;.;T
Eigen
Benign
0.039
Eigen_PC
Benign
0.090
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.81
T;.;.;T;T;T;T;T;.;T
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.29
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.40
T
MutationTaster
Benign
0.86
D;D;D;D;D;D;D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.5
N;N;N;.;.;.;N;N;N;N
REVEL
Uncertain
0.40
Sift
Benign
0.15
T;T;T;.;.;.;T;T;T;T
Sift4G
Benign
0.30
T;T;T;T;T;T;T;T;T;T
Vest4
0.43
MutPred
0.25
.;Gain of glycosylation at T303 (P = 0.0483);.;Gain of glycosylation at T303 (P = 0.0483);.;.;.;.;.;.;
MVP
0.83
MPC
0.72
ClinPred
0.71
D
GERP RS
4.0
gMVP
0.70

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: chr17-41958615; API