Variant 17-43880748-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005374.5(MPP2):c.1093A>G(p.Ser365Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MPP2
NM_005374.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.10

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]

MPP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 link	c.1093A>G	p.Ser365Gly	missense_variant	Exon 10 of 13	ENST00000269095.9	NP_005365.4	Q14168D3DX48

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPP2	ENST00000269095.9 link	c.1093A>G	p.Ser365Gly	missense_variant	Exon 10 of 13	1	NM_005374.5	ENSP00000269095.4		D3DX48
MPP2	ENST00000461854.5 link	c.1165A>G	p.Ser389Gly	missense_variant	Exon 11 of 14	1		ENSP00000428286.1		D3DX49

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251062

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1093A>G (p.S365G) alteration is located in exon 10 (coding exon 9) of the MPP2 gene. This alteration results from a A to G substitution at nucleotide position 1093, causing the serine (S) at amino acid position 365 to be replaced by a glycine (G). 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

0.34

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;.;.;.;T;.;.;.;.;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.97

D;.;.;D;D;D;D;D;.;D

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.72

D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.89

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-2.6

D;D;D;.;.;.;D;D;D;D

REVEL

Uncertain

0.31

Sift

Benign

0.033

D;D;D;.;.;.;D;T;D;D

Sift4G

Benign

0.15

T;T;T;T;T;T;T;T;T;T

Vest4

0.79

MVP

0.75

MPC

1.0

ClinPred

0.89

GERP RS

5.0

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over